The document summarizes key findings from three clinical trials (IMpower110, IMpower150, IMpower130) evaluating the efficacy and safety of atezolizumab in combination with chemotherapy or as monotherapy for the first-line treatment of non-small cell lung cancer. The IMpower110 trial found that atezolizumab monotherapy improved overall survival compared to chemotherapy in patients with high PD-L1 expression. The IMpower150 trial evaluated atezolizumab plus chemotherapy versus chemotherapy alone or with bevacizumab. The IMpower130 trial compared atezolizumab plus two chemotherapy regimens. Overall, the results showed that adding atezolizumab to chemotherapy provided clinical benefit over chemotherapy
Optimizing Therapeutic Strategies in Castration-Resistant Prostate Canceri3 Health
This activity will discuss emerging efficacy and safety data on novel therapies for nmCRPC and mCRPC, strategies to manage adverse events, and the role of imaging studies and PSA testing in evaluating treatment response.
1) The AURELIA trial evaluated bevacizumab combined with chemotherapy versus chemotherapy alone for platinum-resistant recurrent ovarian cancer.
2) The trial found that progression-free survival was significantly longer in the bevacizumab combination group compared to the chemotherapy alone group (median 6.7 months vs 3.4 months).
3) Rates of objective response were also significantly higher in the bevacizumab combination group compared to chemotherapy alone (30.9% vs 12.6%).
New Trends in the Management of Metastatic Prostate Cancerflasco_org
This document discusses new trends in the management of metastatic prostate cancer. It begins with an overview of the clinical states of prostate cancer progression. It then presents a case study of an 85-year-old man with extensive bone metastases from prostate cancer who experienced a significant response to docetaxel chemotherapy. The document reviews several major clinical trials that established the role of docetaxel chemotherapy for newly diagnosed metastatic prostate cancer. It discusses factors like disease volume and age that influence decisions about chemotherapy. The role of androgen-targeted therapies like abiraterone and enzalutamide both before and after chemotherapy is examined. Limitations in the effectiveness of these therapies are presented. The potential for biomarkers like AR-V7 to
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC (Part II)Mohammed Fathy
1) The document discusses targeted therapies for non-small cell lung cancer (NSCLC) with ALK translocations, including crizotinib, alectinib, brigatinib, ceritinib, and lorlatinib.
2) Alectinib is now considered the preferred first-line treatment for ALK-positive NSCLC based on Phase III trials showing it is more effective than crizotinib.
3) For patients who progress on a first-generation ALK inhibitor like crizotinib, later-generation ALK inhibitors such as ceritinib, brigatinib, and lorlatinib have demonstrated efficacy in clinical trials as subsequent therapies.
This document discusses optimal sequencing in metastatic castration-resistant prostate cancer (mCRPC). It presents several case studies and discusses the role of radiation, surgery, nuclear medicine, and systemic therapies. It then addresses questions about standard of care options for mCRPC, including chemotherapy, chemotherapy plus androgen deprivation therapy, chemotherapy plus antiandrogen therapy, and PARP inhibitors. Clinical trials evaluating treatments like cabazitaxel, abiraterone, and enzalutamide in mCRPC are also summarized.
This document discusses locally advanced high risk prostate cancer and evolving treatment options. It provides an overview of risk stratification, guidelines for biopsy from the European Association of Urology, options for imaging with multiparametric MRI, and options for treatment including radical prostatectomy, radiation therapy, and hormonal therapy. New advances in radiation therapy include stereotactic body radiation therapy and hypofractionated regimens. Advances in hormonal therapy include gonadotropin-releasing hormone antagonists and oral options like relugolix. Neoadjuvant docetaxel chemotherapy is also discussed for high risk localized disease.
This document summarizes treatment approaches for metastatic castration-resistant prostate cancer (mCRPC). It discusses definitions of CRPC and mechanisms of resistance. For mCRPC patients with PSADT >10 months and no symptoms, secondary hormonal therapies are recommended, while those with PSADT <10 months receive second-generation antiandrogens. Docetaxel remains first-line for symptomatic mCRPC, while abiraterone, enzalutamide, radium-223, and sipuleucel-T are also options. Detection of AR-V7 in circulating tumor cells may help determine if taxanes or AR-targeted therapies are most suitable. Ongoing treatment, monitoring of
Optimizing Therapeutic Strategies in Castration-Resistant Prostate Canceri3 Health
This activity will discuss emerging efficacy and safety data on novel therapies for nmCRPC and mCRPC, strategies to manage adverse events, and the role of imaging studies and PSA testing in evaluating treatment response.
1) The AURELIA trial evaluated bevacizumab combined with chemotherapy versus chemotherapy alone for platinum-resistant recurrent ovarian cancer.
2) The trial found that progression-free survival was significantly longer in the bevacizumab combination group compared to the chemotherapy alone group (median 6.7 months vs 3.4 months).
3) Rates of objective response were also significantly higher in the bevacizumab combination group compared to chemotherapy alone (30.9% vs 12.6%).
New Trends in the Management of Metastatic Prostate Cancerflasco_org
This document discusses new trends in the management of metastatic prostate cancer. It begins with an overview of the clinical states of prostate cancer progression. It then presents a case study of an 85-year-old man with extensive bone metastases from prostate cancer who experienced a significant response to docetaxel chemotherapy. The document reviews several major clinical trials that established the role of docetaxel chemotherapy for newly diagnosed metastatic prostate cancer. It discusses factors like disease volume and age that influence decisions about chemotherapy. The role of androgen-targeted therapies like abiraterone and enzalutamide both before and after chemotherapy is examined. Limitations in the effectiveness of these therapies are presented. The potential for biomarkers like AR-V7 to
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC (Part II)Mohammed Fathy
1) The document discusses targeted therapies for non-small cell lung cancer (NSCLC) with ALK translocations, including crizotinib, alectinib, brigatinib, ceritinib, and lorlatinib.
2) Alectinib is now considered the preferred first-line treatment for ALK-positive NSCLC based on Phase III trials showing it is more effective than crizotinib.
3) For patients who progress on a first-generation ALK inhibitor like crizotinib, later-generation ALK inhibitors such as ceritinib, brigatinib, and lorlatinib have demonstrated efficacy in clinical trials as subsequent therapies.
This document discusses optimal sequencing in metastatic castration-resistant prostate cancer (mCRPC). It presents several case studies and discusses the role of radiation, surgery, nuclear medicine, and systemic therapies. It then addresses questions about standard of care options for mCRPC, including chemotherapy, chemotherapy plus androgen deprivation therapy, chemotherapy plus antiandrogen therapy, and PARP inhibitors. Clinical trials evaluating treatments like cabazitaxel, abiraterone, and enzalutamide in mCRPC are also summarized.
This document discusses locally advanced high risk prostate cancer and evolving treatment options. It provides an overview of risk stratification, guidelines for biopsy from the European Association of Urology, options for imaging with multiparametric MRI, and options for treatment including radical prostatectomy, radiation therapy, and hormonal therapy. New advances in radiation therapy include stereotactic body radiation therapy and hypofractionated regimens. Advances in hormonal therapy include gonadotropin-releasing hormone antagonists and oral options like relugolix. Neoadjuvant docetaxel chemotherapy is also discussed for high risk localized disease.
This document summarizes treatment approaches for metastatic castration-resistant prostate cancer (mCRPC). It discusses definitions of CRPC and mechanisms of resistance. For mCRPC patients with PSADT >10 months and no symptoms, secondary hormonal therapies are recommended, while those with PSADT <10 months receive second-generation antiandrogens. Docetaxel remains first-line for symptomatic mCRPC, while abiraterone, enzalutamide, radium-223, and sipuleucel-T are also options. Detection of AR-V7 in circulating tumor cells may help determine if taxanes or AR-targeted therapies are most suitable. Ongoing treatment, monitoring of
This document summarizes the liver stereotactic body radiation therapy (SBRT) techniques used to treat hepatocellular carcinoma (HCC) and liver metastases at Meenakshi Mission Hospital & Research Centre. Key points include:
1) Liver SBRT is used for 3 or fewer lesions 7cm or less in non-cirrhotic or cirrhotic livers, with controlled extrahepatic disease and a treatment history of local/regional/systemic therapies.
2) Treatment plans aim to spare at least 35% of the liver from the high SBRT doses to avoid liver decompensation. Special considerations are made for cirrhotic livers.
3) Treatments utilize respiratory motion management,
This document summarizes recent advances in treating triple negative breast cancer (TNBC). TNBC accounts for 15-20% of breast cancers and has a poorer prognosis than other subtypes. New classifications identify basal-like and other subtypes. Standard chemotherapy remains the first-line treatment for early and advanced TNBC, but adding platinum agents or nab-paclitaxel to neoadjuvant chemotherapy improves outcomes. PARP inhibitors such as olaparib and talazoparib improve progression-free survival in BRCA-mutated metastatic TNBC. Immunotherapy with atezolizumab, pembrolizumab or combinations improves progression-free and overall survival in PD-L1 positive advanced
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
ADC’s - What Everyone with MBC Should Know about Antibody Drug Conjugatesbkling
Antibody drug conjugates (ADC’s), a novel class of anticancer agents, have been around for decades but recently great strides have been made in metastatic breast cancer. Next generation ADC’s, sometimes referred to as ' Trojan Horses' have shown promising efficacy in all subtypes of MBC. Join Dr. Erika Hamilton, Director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, and partner with Tennessee Oncology PLCC, as she presents an overview of ADC’s, biomarkers and clinical mapping, current treatment options, as well as the promising trials to keep an eye on. There will be time for your questions throughout the presentation.
This document discusses targeted therapy for breast cancer. It begins by providing background on declining mortality rates for breast cancer over time. It then discusses how cancers develop multiple alterations that allow uncontrolled growth and outlines six essential alterations in cell physiology that contribute to malignancy. The document discusses molecular alterations that occur in breast cancer progression. It defines targeted therapy as drugs that target uniquely disrupted pathways in cancer cells. The document outlines several targeted therapies for breast cancer including hormonal therapies like tamoxifen, aromatase inhibitors, and fulvestrant. It discusses clinical trials demonstrating the benefits of these therapies. It also discusses therapies that target the HER2 receptor like trastuzumab and lapatinib. In summary, the document provides an overview of targeted
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC Part IMohammed Fathy
1) Chemotherapy provides a modest survival benefit for early stage NSCLC based on multiple randomized trials. The absolute improvement in 5-year survival is approximately 5%.
2) The IALT trial showed a 4% improvement in 5-year survival with cisplatin-based chemotherapy compared to observation alone for stage I-III NSCLC.
3) The JBR.10 trial demonstrated an 11% absolute improvement in 5-year survival with vinorelbine and cisplatin compared to observation for stage IB-II NSCLC. However, the benefit was largely seen in stage II patients.
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
Advances in management of castration resistant prostate cancerAlok Gupta
Given this patient's advanced age and comorbidities, I would recommend abiraterone acetate as the second line treatment option post enzalutamide progression. Abiraterone has shown survival benefit with good tolerability in older patients with comorbidities in the COU-AA-301 trial. Cabazitaxel could be considered but may have higher toxicity risks in this patient. Close monitoring would be needed.
Describes the emerging resistance of epithelial cancer of the ovary to current therapies and the role of PARP inhibitors in the management in view of the recent drug approvals.
Radiation therapy plays an evolving role in the treatment of lung cancer beyond just causing DNA double strand breaks.
1) Stereotactic body radiation therapy (SBRT) can provide curative treatment for early stage lung cancer with high local control rates.
2) For locally advanced lung cancer, dose escalation with conventional fractionation in RTOG 0617 did not improve overall survival, highlighting the importance of fractionation and sequencing with other therapies.
3) Radiation induces tumor cell death that can elicit anti-tumor immune responses, known as abscopal effects, especially when combined with immunotherapy like anti-CTLA4 and anti-PD1/PDL1 agents which play complementary roles.
Lorlatinib shows efficacy in treating ALK-positive and ROS1-positive non-small cell lung cancer (NSCLC) in patients who have failed earlier treatments. In a study of 200 NSCLC patients treated with lorlatinib, the disease control rate was 86% for ALK-positive patients and 88% for ROS1-positive patients. Lorlatinib also achieved high response rates in central nervous system metastases of 41.7% for ALK-positive patients and 53.3% for ROS1-positive patients. Median progression-free survival was 11.8 months for ALK-positive patients and 7.6 months for ROS1-positive patients. Lorlatinib demonstrated clinical benefit in treating advanced AL
Poly-ADP-ribose polymerase inhibitors (PARPis) are the most active and interesting therapies approved for the treatment of epithelial ovarian cancer. They have changed the clinical management of a disease characterized, in almost half of cases, by extreme genetic complexity and alteration of DNA damage repair pathways, particularly homologous recombination (HR) deficiency. It is causing a paradigm shift in the first-line treatment of patients with advanced ovarian cancer
Recent advances in targeted therapy for metastatic lung cancerAlok Gupta
This document discusses recent advances in targeted therapy for metastatic lung cancer. It summarizes key findings from several clinical trials evaluating third-generation EGFR TKIs like osimertinib for patients with EGFR mutation-positive NSCLC. The document highlights that osimertinib provides significantly longer progression-free survival compared to earlier generation EGFR TKIs, with a median PFS of 18.9 months versus 10.2 months. Osimertinib also demonstrated a higher objective response rate and longer duration of response. Benefits were consistent across patient subgroups.
1) The document discusses management of advanced prostate cancer, focusing on high risk disease. Treatment options for high risk prostate cancer include radiotherapy, androgen deprivation therapy, surgery, or a combination approach.
2) Studies have shown that dose escalated external beam radiotherapy improves outcomes for high risk prostate cancer when combined with androgen deprivation therapy. Moderate hypofractionation is a reasonable alternative to standard fractionation.
3) For high risk disease, long term androgen deprivation therapy of 2 years or more is superior to short term therapy when combined with radiotherapy. However, reducing the duration of long term androgen deprivation may be considered.
Concomitant chemotherapy provides the greatest benefit for patients with locally advanced head and neck cancer according to the MACHNC 2021 meta-analysis. It improves 5-year overall survival by 6.5% and event-free survival by 5.8%, with the greatest decrease in locoregional failure rates. Induction chemotherapy provides smaller benefits of 2.2% for overall survival and 1.45% for event-free survival, as well as a significant decrease in distant failure rates. Adjuvant chemotherapy does not improve survival and increases 120-day mortality. Cisplatin-based regimens are preferred for concomitant and induction chemotherapy. This may be the final MACHNC analysis as no new patients have been
1) A landmark randomized clinical trial published in 1999 found that concurrent weekly cisplatin chemotherapy during pelvic radiation improved progression-free survival and overall survival rates for patients with bulky stage IB cervical cancer compared to radiation alone. The study demonstrated a 79% 5-year progression-free survival rate and 85% 5-year overall survival rate for patients receiving concurrent chemoradiation versus 74% and 63% respectively for radiation alone.
2) Another 1999 randomized clinical trial found that for high-risk cervical cancer patients, pelvic radiation with concurrent cisplatin and fluorouracil chemotherapy resulted in improved overall survival compared to pelvic and para-aortic radiation alone, establishing concurrent chemoradiation as the new standard
The document summarizes several clinical trials related to prostate cancer treatment. It provides details on trials such as PIVOT, ProtecT, TAX327 which compared radical prostatectomy vs observation, active monitoring vs surgery or radiation, and docetaxel vs mitoxantrone for advanced prostate cancer. It also summarizes larger ongoing trials like STAMPEDE and LATITUDE that are evaluating multiple treatment strategies for high risk or metastatic prostate cancer.
4-yr OS after 2nd-line Nivolumab, pooled analysis (based on Scott Antonia pre...Mauricio Lema
This document discusses long-term survival outcomes with nivolumab treatment in patients with previously treated advanced non-small cell lung cancer. It finds that early disease control, defined as stable or shrinking tumors after 3 months of treatment, as well as achieving an objective response, are associated with improved long-term survival. Patients who achieved early disease control had a median overall survival of 49.2 months compared to 11.3 months for those without early disease control. Similarly, patients who achieved an objective response had a median overall survival of not reached compared to 11.4 months for non-responders. The study demonstrates that nivolumab provides long-term survival benefits in this patient population.
Lung cancer is the leading cause of cancer death worldwide. Bevacizumab, when added to chemotherapy, has shown improved outcomes for non-small cell lung cancer (NSCLC) patients in several phase III trials. The E4599 trial demonstrated a significant overall survival benefit of bevacizumab plus carboplatin and paclitaxel compared to chemotherapy alone. Subsequent observational studies confirmed these clinical benefits. Ongoing studies are exploring immunotherapy combinations that further improve outcomes for NSCLC patients.
This document summarizes the liver stereotactic body radiation therapy (SBRT) techniques used to treat hepatocellular carcinoma (HCC) and liver metastases at Meenakshi Mission Hospital & Research Centre. Key points include:
1) Liver SBRT is used for 3 or fewer lesions 7cm or less in non-cirrhotic or cirrhotic livers, with controlled extrahepatic disease and a treatment history of local/regional/systemic therapies.
2) Treatment plans aim to spare at least 35% of the liver from the high SBRT doses to avoid liver decompensation. Special considerations are made for cirrhotic livers.
3) Treatments utilize respiratory motion management,
This document summarizes recent advances in treating triple negative breast cancer (TNBC). TNBC accounts for 15-20% of breast cancers and has a poorer prognosis than other subtypes. New classifications identify basal-like and other subtypes. Standard chemotherapy remains the first-line treatment for early and advanced TNBC, but adding platinum agents or nab-paclitaxel to neoadjuvant chemotherapy improves outcomes. PARP inhibitors such as olaparib and talazoparib improve progression-free survival in BRCA-mutated metastatic TNBC. Immunotherapy with atezolizumab, pembrolizumab or combinations improves progression-free and overall survival in PD-L1 positive advanced
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
ADC’s - What Everyone with MBC Should Know about Antibody Drug Conjugatesbkling
Antibody drug conjugates (ADC’s), a novel class of anticancer agents, have been around for decades but recently great strides have been made in metastatic breast cancer. Next generation ADC’s, sometimes referred to as ' Trojan Horses' have shown promising efficacy in all subtypes of MBC. Join Dr. Erika Hamilton, Director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, and partner with Tennessee Oncology PLCC, as she presents an overview of ADC’s, biomarkers and clinical mapping, current treatment options, as well as the promising trials to keep an eye on. There will be time for your questions throughout the presentation.
This document discusses targeted therapy for breast cancer. It begins by providing background on declining mortality rates for breast cancer over time. It then discusses how cancers develop multiple alterations that allow uncontrolled growth and outlines six essential alterations in cell physiology that contribute to malignancy. The document discusses molecular alterations that occur in breast cancer progression. It defines targeted therapy as drugs that target uniquely disrupted pathways in cancer cells. The document outlines several targeted therapies for breast cancer including hormonal therapies like tamoxifen, aromatase inhibitors, and fulvestrant. It discusses clinical trials demonstrating the benefits of these therapies. It also discusses therapies that target the HER2 receptor like trastuzumab and lapatinib. In summary, the document provides an overview of targeted
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC Part IMohammed Fathy
1) Chemotherapy provides a modest survival benefit for early stage NSCLC based on multiple randomized trials. The absolute improvement in 5-year survival is approximately 5%.
2) The IALT trial showed a 4% improvement in 5-year survival with cisplatin-based chemotherapy compared to observation alone for stage I-III NSCLC.
3) The JBR.10 trial demonstrated an 11% absolute improvement in 5-year survival with vinorelbine and cisplatin compared to observation for stage IB-II NSCLC. However, the benefit was largely seen in stage II patients.
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
Advances in management of castration resistant prostate cancerAlok Gupta
Given this patient's advanced age and comorbidities, I would recommend abiraterone acetate as the second line treatment option post enzalutamide progression. Abiraterone has shown survival benefit with good tolerability in older patients with comorbidities in the COU-AA-301 trial. Cabazitaxel could be considered but may have higher toxicity risks in this patient. Close monitoring would be needed.
Describes the emerging resistance of epithelial cancer of the ovary to current therapies and the role of PARP inhibitors in the management in view of the recent drug approvals.
Radiation therapy plays an evolving role in the treatment of lung cancer beyond just causing DNA double strand breaks.
1) Stereotactic body radiation therapy (SBRT) can provide curative treatment for early stage lung cancer with high local control rates.
2) For locally advanced lung cancer, dose escalation with conventional fractionation in RTOG 0617 did not improve overall survival, highlighting the importance of fractionation and sequencing with other therapies.
3) Radiation induces tumor cell death that can elicit anti-tumor immune responses, known as abscopal effects, especially when combined with immunotherapy like anti-CTLA4 and anti-PD1/PDL1 agents which play complementary roles.
Lorlatinib shows efficacy in treating ALK-positive and ROS1-positive non-small cell lung cancer (NSCLC) in patients who have failed earlier treatments. In a study of 200 NSCLC patients treated with lorlatinib, the disease control rate was 86% for ALK-positive patients and 88% for ROS1-positive patients. Lorlatinib also achieved high response rates in central nervous system metastases of 41.7% for ALK-positive patients and 53.3% for ROS1-positive patients. Median progression-free survival was 11.8 months for ALK-positive patients and 7.6 months for ROS1-positive patients. Lorlatinib demonstrated clinical benefit in treating advanced AL
Poly-ADP-ribose polymerase inhibitors (PARPis) are the most active and interesting therapies approved for the treatment of epithelial ovarian cancer. They have changed the clinical management of a disease characterized, in almost half of cases, by extreme genetic complexity and alteration of DNA damage repair pathways, particularly homologous recombination (HR) deficiency. It is causing a paradigm shift in the first-line treatment of patients with advanced ovarian cancer
Recent advances in targeted therapy for metastatic lung cancerAlok Gupta
This document discusses recent advances in targeted therapy for metastatic lung cancer. It summarizes key findings from several clinical trials evaluating third-generation EGFR TKIs like osimertinib for patients with EGFR mutation-positive NSCLC. The document highlights that osimertinib provides significantly longer progression-free survival compared to earlier generation EGFR TKIs, with a median PFS of 18.9 months versus 10.2 months. Osimertinib also demonstrated a higher objective response rate and longer duration of response. Benefits were consistent across patient subgroups.
1) The document discusses management of advanced prostate cancer, focusing on high risk disease. Treatment options for high risk prostate cancer include radiotherapy, androgen deprivation therapy, surgery, or a combination approach.
2) Studies have shown that dose escalated external beam radiotherapy improves outcomes for high risk prostate cancer when combined with androgen deprivation therapy. Moderate hypofractionation is a reasonable alternative to standard fractionation.
3) For high risk disease, long term androgen deprivation therapy of 2 years or more is superior to short term therapy when combined with radiotherapy. However, reducing the duration of long term androgen deprivation may be considered.
Concomitant chemotherapy provides the greatest benefit for patients with locally advanced head and neck cancer according to the MACHNC 2021 meta-analysis. It improves 5-year overall survival by 6.5% and event-free survival by 5.8%, with the greatest decrease in locoregional failure rates. Induction chemotherapy provides smaller benefits of 2.2% for overall survival and 1.45% for event-free survival, as well as a significant decrease in distant failure rates. Adjuvant chemotherapy does not improve survival and increases 120-day mortality. Cisplatin-based regimens are preferred for concomitant and induction chemotherapy. This may be the final MACHNC analysis as no new patients have been
1) A landmark randomized clinical trial published in 1999 found that concurrent weekly cisplatin chemotherapy during pelvic radiation improved progression-free survival and overall survival rates for patients with bulky stage IB cervical cancer compared to radiation alone. The study demonstrated a 79% 5-year progression-free survival rate and 85% 5-year overall survival rate for patients receiving concurrent chemoradiation versus 74% and 63% respectively for radiation alone.
2) Another 1999 randomized clinical trial found that for high-risk cervical cancer patients, pelvic radiation with concurrent cisplatin and fluorouracil chemotherapy resulted in improved overall survival compared to pelvic and para-aortic radiation alone, establishing concurrent chemoradiation as the new standard
The document summarizes several clinical trials related to prostate cancer treatment. It provides details on trials such as PIVOT, ProtecT, TAX327 which compared radical prostatectomy vs observation, active monitoring vs surgery or radiation, and docetaxel vs mitoxantrone for advanced prostate cancer. It also summarizes larger ongoing trials like STAMPEDE and LATITUDE that are evaluating multiple treatment strategies for high risk or metastatic prostate cancer.
4-yr OS after 2nd-line Nivolumab, pooled analysis (based on Scott Antonia pre...Mauricio Lema
This document discusses long-term survival outcomes with nivolumab treatment in patients with previously treated advanced non-small cell lung cancer. It finds that early disease control, defined as stable or shrinking tumors after 3 months of treatment, as well as achieving an objective response, are associated with improved long-term survival. Patients who achieved early disease control had a median overall survival of 49.2 months compared to 11.3 months for those without early disease control. Similarly, patients who achieved an objective response had a median overall survival of not reached compared to 11.4 months for non-responders. The study demonstrates that nivolumab provides long-term survival benefits in this patient population.
Lung cancer is the leading cause of cancer death worldwide. Bevacizumab, when added to chemotherapy, has shown improved outcomes for non-small cell lung cancer (NSCLC) patients in several phase III trials. The E4599 trial demonstrated a significant overall survival benefit of bevacizumab plus carboplatin and paclitaxel compared to chemotherapy alone. Subsequent observational studies confirmed these clinical benefits. Ongoing studies are exploring immunotherapy combinations that further improve outcomes for NSCLC patients.
1) Bevacizumab is an anti-angiogenic drug that has shown efficacy in improving progression-free survival and overall survival when added to chemotherapy for first-line treatment of non-squamous non-small cell lung cancer based on results from phase 3 trials.
2) The IMpower150 trial found that adding atezolizumab, an immune checkpoint inhibitor, to bevacizumab and chemotherapy further improved progression-free and overall survival compared to bevacizumab and chemotherapy alone in previously untreated non-squamous non-small cell lung cancer.
3) The NEJ026 trial found that adding bevacizumab to erlotinib, an EGFR tyrosine kinase inhibitor, significantly improved
This document summarizes updated overall survival (OS) data from the IMpower150 study, which evaluated the combination of atezolizumab, bevacizumab, and chemotherapy compared to chemotherapy plus bevacizumab alone in previously untreated non-squamous non-small cell lung cancer. Baseline characteristics were balanced across study arms. Statistically significant and clinically meaningful improvements in progression-free survival with the triple combination were previously reported and continued with additional follow-up. This presentation focuses on interim OS data in the overall study population and key subgroups.
The document discusses lung cancer subtypes and molecular features that can guide treatment. It provides statistics on the distribution of histology types among lung cancer cases. It also summarizes several key studies investigating targeted therapies such as EGFR TKIs versus chemotherapy as first-line treatment for advanced non-small cell lung cancer, noting improved progression-free survival with TKIs in patients with EGFR mutations. Molecular testing is increasingly important for determining personalized treatment approaches in lung cancer.
3.Case Based Moderation Slidedeck 110_130_150.pptxBipineshSansar
This document discusses treatment options for patients with metastatic non-small cell lung cancer (NSCLC) without driver mutations. First-line options include cancer immunotherapy (CIT) monotherapy, CIT plus chemotherapy, CIT plus chemotherapy plus anti-VEGF. Second-line options include chemotherapy, CIT doublet, or anti-angiogenic plus chemotherapy. CIT is not an option in later lines if already given in earlier lines. The document also discusses predictive biomarkers for CIT efficacy and immune checkpoint inhibitors.
Advances in Immunotherapy for Non-Small Cell Lung Cancerflasco_org
This document summarizes advances in immunotherapy for non-small cell lung cancer (NSCLC). It discusses results from key clinical trials of immunotherapy in both first-line and second-line settings for advanced NSCLC. It also reviews studies combining immunotherapy with chemotherapy, including evidence that combinations can provide benefits over chemotherapy alone. Emerging data on biomarkers like tumor mutational burden are presented. Future areas of research highlighted include neoadjuvant studies and investigating immunotherapy mechanisms through translational research.
The document provides guidelines for the treatment of advanced non-small cell lung cancer. It recommends that first-line therapy should consist of platinum-based combination chemotherapy for patients with good performance status. For patients with EGFR mutations, an EGFR tyrosine kinase inhibitor is the preferred first-line treatment. It also recommends the addition of bevacizumab or cetuximab to platinum-based chemotherapy for certain patients.
This document discusses a clinical trial comparing cisplatin-based chemoradiotherapy to cetuximab-based chemoradiotherapy for p16-positive oropharyngeal cancer. The trial found that while overall toxicity was similar between the two arms, serious adverse events were significantly more common with cisplatin treatment. However, patients receiving cisplatin chemoradiotherapy experienced significantly better 2-year overall survival and lower recurrence rates compared to those receiving cetuximab chemoradiotherapy. The findings suggest that for HPV-positive oropharyngeal cancer, cisplatin chemoradiotherapy provides excellent survival outcomes despite greater toxicity risks compared to cetuximab chemoradiotherapy.
This document summarizes evidence for adjuvant and neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC). Meta-analyses show adjuvant cisplatin-based chemotherapy improves 5-year survival by 4-5% after surgery for stages II-III NSCLC. Individual trials also found benefits, though some only for certain stages. Neoadjuvant chemotherapy may improve survival by 5% at 5 years for resectable stage IIIA NSCLC. Ongoing trials aim to personalize chemotherapy based on biomarkers and add targeted therapies.
This document summarizes evidence for adjuvant and neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC). Meta-analyses show adjuvant cisplatin-based chemotherapy improves 5-year survival by 4-5% after surgery for stages II-III NSCLC. Individual trials also found benefits, though some only for certain stages. Neoadjuvant chemotherapy may improve survival by 5% at 5 years for resectable stage IIIA NSCLC. Ongoing trials aim to personalize chemotherapy based on biomarkers and add targeted therapies.
This document provides an overview of evolving understanding of biomarkers for response to immune checkpoint inhibition in non-small cell lung cancer (NSCLC). Key points include:
1) Clinical benefit of immunotherapy is seen across all levels of PD-L1 expression, including in patients with <1% PD-L1 expression, though benefit increases with higher PD-L1 levels.
2) Tumor mutational burden (TMB) and PD-L1 expression identify distinct patient populations.
3) PD-L1 testing has limitations due to intratumoral heterogeneity and potential sampling errors from small biopsies.
4) Several studies demonstrate superior outcomes for first-line pembrolizumab or ate
1) Lung cancer tumors display a high number of somatic mutations, rendering them more immunogenic. The presence of tumor-infiltrating FOXP3+ regulatory T-cells is associated with recurrence in early-stage non-small cell lung cancer patients.
2) Brambilla et al. (2016) found that lymphocyte infiltration has a prognostic effect in resectable non-small cell lung cancer.
3) Immunotherapies targeting CTLA-4 and PD-1/PD-L1 have shown efficacy in lung cancer treatment, with nivolumab demonstrating improved overall survival compared to docetaxel in previously treated squamous and non-squamous non-small cell lung cancer
Selective Use Of Postoperative Radiotherapy AftEr MastectOmyfondas vakalis
The SUPREMO trial aims to determine whether postmastectomy radiotherapy (PMRT) improves outcomes for women with early-stage breast cancer with 1-3 positive lymph nodes. The trial will randomize approximately 3,500 patients to receive either chest wall irradiation or no chest wall irradiation after mastectomy and systemic therapy. The primary outcome is overall survival, with secondary outcomes including disease-free survival, acute/late morbidity, quality of life, and cost-effectiveness. Results from previous trials suggest PMRT may reduce locoregional recurrence and improve survival, especially for those with more positive nodes, but more evidence is still needed.
1) Non-small cell lung cancer (NSCLC) accounts for 85-90% of lung cancers, with 10-15% being small cell lung cancer (SCLC). NSCLC can be divided into squamous cell carcinoma and non-squamous cell carcinoma.
2) Approximately 25-40% of patients with NSCLC present with locally advanced (Stage III) disease which has a low 5-year survival rate. Around 30% present with unresectable Stage III disease.
3) The KEYNOTE-189 trial showed that pembrolizumab plus chemotherapy improved overall survival compared to placebo plus chemotherapy as first-line treatment for Stage IV non-squamous NSCLC, regardless of PD-L1 expression
This document discusses treatment options for advanced non-small cell lung cancer (NSCLC). It summarizes findings from clinical trials comparing chemotherapy drugs and combinations, and evaluates the benefits of adding targeted therapies like bevacizumab and EGFR inhibitors to chemotherapy. Key results showed that platinum-based doublet chemotherapy improves survival compared to best supportive care, and adding bevacizumab to paclitaxel and carboplatin further improves outcomes. Studies also found EGFR inhibitors gefitinib and erlotinib provide benefits for NSCLC patients with EGFR mutations.
Lung cancer is a leading cause of cancer death. Immunotherapy using immune checkpoint inhibitors that target proteins like PD-1 and PD-L1 has shown promise in treating lung cancer. A study presented at ASCO 2015 found that treatment with the PD-L1 inhibitor atezolizumab resulted in improved survival for NSCLC patients with higher levels of PD-L1 expression on tumor cells compared to docetaxel chemotherapy. Another study showed nivolumab, a PD-1 inhibitor, improved survival over docetaxel as a treatment for advanced non-squamous NSCLC after chemotherapy, with greater benefit seen in patients with higher PD-L1 expression levels. These results suggest PD-L1 expression can help identify
1) Adjuvant chemotherapy reduces breast cancer mortality by 17-33% according to meta-analyses, with anthracycline-based regimens being more effective than CMF.
2) For HER2-positive early breast cancer, adjuvant chemotherapy plus trastuzumab is the standard of care, improving disease-free and overall survival compared to chemotherapy alone.
3) For endocrine-responsive early breast cancer, the absolute benefit of chemotherapy depends on risk factors; genomic signatures can help identify patients most likely to benefit from chemotherapy in addition to endocrine therapy.
1) Adjuvant chemotherapy reduces breast cancer mortality by 17-33% according to meta-analyses, with anthracycline-based regimens being more effective than CMF.
2) For HER2-positive early breast cancer, adjuvant chemotherapy plus trastuzumab is the standard of care, improving disease-free and overall survival compared to chemotherapy alone.
3) For endocrine-responsive early breast cancer, the absolute benefit of chemotherapy depends on risk factors; genomic signatures can help identify patients most likely to benefit from chemotherapy in addition to endocrine therapy.
Abiraterone acetate plus low-dose prednisone was shown to have a favorable safety profile and improve outcomes for men with metastatic castration-resistant prostate cancer progressing after docetaxel-based chemotherapy. The study found that abiraterone acetate plus prednisone extended overall survival by a median of 14.8 months compared to 10.9 months for placebo, improved time to PSA progression, and reduced the risk of death by 35% compared to placebo. The most common side effects were decreased lymphocyte levels and increased liver enzymes, and abiraterone acetate demonstrated less fatigue, back pain, and spinal cord compression than placebo. The results suggest abiraterone acetate is an effective option
Similar to 1. Tecentriq 1L NSCLC- IMpower110-130-150 RIPE Deck FINAL.pptx (20)
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
2. Table of content
• Disease background- NSCLC
• Evolving landscape of lung cancer treatment
• IMpower 110 study
• IMpower 150 study
• IMpower 130 study
• Summary
3. Introduction: Non-small cell lung cancer1-8
1. Pikor, et al. Lung Cancer 2013; 2. Howlader, et al. SEER Cancer Statistics Review 2016; 3. Carter, et al. RadioGraphics
2014; 4. American Cancer Society 2016: NSCLC; 5. Varghese, et al. J Thorac Oncol 2014; 6. Vavala, et al. Curr Respir
Care Rep 2014; 7. Pelosof, et al. JNCI 2017; 8. Dempke. Anticancer Research 2015
01
Slower growing tumour with varying
initial ORR according to driver
mutation/targeted therapy
02
NSCLC accounts for about 80–85%
of all lung cancers
03
~15% of patients with NSCLC are
never smokers
04
Median age of 70 years and typically
present with cough, chest pain and
dyspnoea
05
Metastasis occurs later in the
disease process:
55% of patients have distant disease
at diagnosis
06
Targeted agents have improved
survival rates
in NSCLC patients with driver mutations
4. Evolving landscape of lung cancer treatment1
1980s 2000s 2015+
NSCLC vs SCLC
Chemotherapy
Chemotherapy
± anti-angiogenics Targeted therapy Cancer immunotherapy
Histological subtype
Molecular pathology (EGFR / ALK / ROS1 / BRAF)
Checkpoint inhibition
1. Figure adapted from Pao, et al. Lancet Oncol 2011
5. There is an unmet need in the treatment of patients with
NSCLC with no actionable biomarker
1. Gutierrez, et al. Clin Lung Cancer 2017; 2. Barlesi, et al. Lancet 2016
Molecular profiling of 17,664 patients with NSCLC by the
French Cooperative Thoracic Intergroup (IFCT)2
Overall survival stratified by therapy type (N = 805)
in patients with NSCLC1
However, a significant
portion of patients with
NSCLC have no known
actionable biomarker
KRAS
29%
EGFR
11%
HER2
1%
ALK
5%
PI3K
2%
Unknown
35%
Full WT
15% BRAF
2%
5.1 31.8
1.0
0.8
0.6
0.4
0.2
0
0
Time (months)
OS
estimate
36
12
6 24 30
18 42 48
12.7
Targeted therapies
have improved
outcomes in NSCLC
Targeted therapy (n=131)
Non-targeted cytotoxic
therapy (n=482)
Observation (n=192)
Targeted therapy vs
non-targeted therapy
HR=0.47 (95% CI: 0.36–0.63)
P<0.0001
6. Global phase III studies of Atezolizumab in first-line
treatment of NSCLC
1L
mNSCLC
Arm A
Atezolizumab
Arm B
Carbo/Cis + Pem (Non-squamous)
Carbo/Cis + Gem (Squamous)
Non-squamous and
squamous
N=572
NCT02409342
R
• IMpower110: Is atezolizumab monotherapy, a
better agent than chemotherapy in PD-L1 selected
chemotherapy-naive patients?
Arm A
Atezolizumab + Carbo/Nab-Pac
Arm B
Carbo/Nab-Pac
Non-squamous
ITT: N=723
ITT-WT: N=679
NCT02367781
R
• IMpower130: Is a steroid-sparing
chemotherapy regimen a better combination
partner for atezolizumab?
Arm A
Atezolizumab + Carbo/Pac
Arm B
Atezolizumab + Carbo/Pac/Bev
Arm C
Carbo/Pac/Bev
Non-squamous
N=1202
NCT02366143
R
• IMpower150: Does the addition of atezolizumab
to the SoC bevacizumab plus paclitaxel and
carboplatin add clinical benefit? Is there
improved clinical benefit if bevacizumab is
replaced by atezolizumab?
7. IMpower110 (Squamous & non-squamous NSCLC)
Atezolizumab monotherapy compared with a Platinum Agent (Cisplatin or Carboplatin) +
(Pemetrexed or Gemcitabine) in IL NSCLC
8. NON-SQUAMOUS: Carboplatin
or cisplatin + pemetrexed¶
SQUAMOUS: Carboplatin or
cisplatin + gemcitabineǁ
IMpower110: a randomised, phase III, multicentre study
Spigel, et al. ESMO 2019 (Abs LBA78)
Survival
follow-up
Stage IV non-squamous
or squamous NSCLC
Chemotherapy naïve
PD-L1 selected*
EGFR/ALK negative
Stratification factors:
• Sex
• ECOG PS
• Histology
• PD-L1 IHC expression‡
N=572§
Maintenance
(no crossover permitted)
4 or 6 cycles
R
1:1
PD or loss of
clinical
benefit**
PD‡‡
NON-SQUAMOUS:
pemetrexed
SQUAMOUS:
Best Supportive Care
Atezolizumab
1200 mg q3w
Primary endpoint: OS in WT population
(excluding patients with EGFR+/ALK+ NSCLC)
Key secondary endpoints: investigator-assessed
PFS, ORR and DOR (per RECIST version 1.1)
Atezolizumab
1200 mg q3w
*PD-L1 positive defined as TC1/2/3 or IC1/2/3 (PD-L1 expression ≥1% on TC or IC), with tumour PD-L1 expression determined by IHC
assay (VENTANA SP142 IHC assay) performed by a central laboratory; ‡TC1/2/3 and any IC vs TC0 and IC1/2/3; §554 patients in the
WT population; ¶Cisplatin 75 mg/m2 or carboplatin area under the curve (AUC) 6 + pemetrexed 500 mg/m2 IV q3w; ǁCisplatin 75 mg/m2
+ gemcitabine 1250 mg/m2 or carboplatin AUC 5 + gemcitabine 1000 mg/m2 IV q3w; **Defined as any of the following: signs or
symptoms of PD; decline in ECOG PS; progression at critical anatomical sites that cannot be managed by permitted medical
interventions; ‡‡By RECIST v1.1
9. IMpower110: prevalence of PD-L1 expression*
*PD-L1 status determined using the VENTANA SP142 PD-L1 IHC assay
Data cut-off: 10 September 2018 Spigel, et al. ESMO 2019 (Abs LBA78)
Arm A (atezo) Arm B (chemo)
TC3 or IC3 WT
≥ 50% TC or ≥ 10% IC
Prevalence
(%)
0
10
20
30
40
50
60
70
80
90
100
38.6% 35.4%
59.9% 58.5%
TC1/2/3 or IC1/2/3 WT
≥ 1% TC or IC
TC2/3 or IC2/3 WT
≥ 5% TC or IC
100.0% 100.0%
n=107 n=98 n=166 n=162 n=277 n=277
Prevalence of PD-L1
expression was similar
between treatment arms
10. IMpower110: baseline characteristics
Date cut-off: 10 September 2018
Spigel, et al. ESMO 2019 (Abs LBA78)
Characteristic, n (%)
TC1/2/3 or IC1/2/3 WT TC3 or IC3 WT
Arm A (atezo)
n=277
Arm B (chemo)
n=277
Arm A (atezo)
n=107
Arm B (chemo)
n=98
Age <65 y 143 (51.6) 134 (48.4) 59 (55.1) 43 (43.9)
Male 196 (70.8) 193 (69.7) 79 (73.8) 64 (65.3)
White 227 (81.9) 240 (86.6) 87 (81.3) 82 (83.7)
Asian 45 (16.2) 30 (10.8) 20 (18.7) 15 (15.3)
Never used tobacco 37 (13.4) 35 (12.6) 9 (8.4) 15 (15.3)
Non-squamous histology 192 (69.3) 193 (69.7) 80 (74.8) 75 (76.5)
ECOG PS 0 97 (35.0) 102 (36.8) 35 (32.7) 38 (38.8)
Baseline characteristics were well balanced
between arms and PD-L1 subgroups
11. 50
100
80
60
Overall
Survival
(%)
Months
40
30
10
90
70
20
0
0
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 28 30 32 34 36
94 85 80 66 61 48 40 34 25 18 16 11 6 5 2
89 75 65 50 40 33 28 19 12 9 7 6
26
7
4 3 3 3 1
38
Chemotherapy
107
Atezolizumab
98
Atezolizumab
Chemotherapy
Censored
IMpower110: OS in the TC3/IC3 population
NE, not estimable; *Stratified; ‡Stratified log-rank
Data cut-off: 10 September 2018
Spigel, et al. ESMO 2019 (Abs LBA78)
Median follow-up at
primary analysis,
15.7 mo (range, 0–35)
HR,* 0.59 (95% CI: 0.40, 0.89); P = 0.0106‡
Median OS, 20.2 mo
(95% CI: 16.5, NE)
Median OS, 13.1 mo
(95% CI: 7.4, 16.5)
The primary endpoint of OS in
the PD-L1 high subgroup
was met
Landmark
Arm A (atezo)
n=107
Arm B (chemo)
n=98
6-month OS
(95% CI), %
76.3
(68.2, 84.4)
70.1
(60.8, 79.4)
12-month OS
(95% CI), %
64.9
(55.4, 74.4)
50.6
(40.0, 61.3)
12. IMpower110: OS in key subgroups
(TC3/IC3-WT population)
*The 1 patient in the ≥85 years subgroup is not
included, and 1 patient’s race was unknown;
‡Unstratified; §Stratified
Data cut-off: 10 September 2018
Spigel, et al. ESMO 2019 (Abs LBA78)
‡
§
*
OS benefit observed in all clinically relevant subgroups
13. IMpower110: subsequent treatment
Data cut-off: 10 September 2018 Spigel, et al. ESMO 2019 (Abs LBA78)
Arm A (atezo)
n=277
Arm B (chemo)
n=277
Patients with ≥ 1 therapy, n (%) 82 (29.6) 137 (49.5)
Chemotherapy 77 (27.8) 68 (24.5)
Immunotherapy 7 (2.5) 80 (28.9)
Targeted therapy 14 (5.1) 12 (4.3)
Nearly a third of patients in the control arm
received subsequent cancer immunotherapy
The proportion of patients who received
subsequent chemotherapy or targeted therapy
was similar across the PD-L1 subgroups
14. 100
80
60
Progression-Free
Survival
(%)
Months
40
30
10
90
70
50
20
0
0
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 28 30 32 34 36
82 72 60 45 31 25 21 16 13 10 8 4 4 2
74 62 36 26 16 13 8 5 5 1 1 1
26
4
38
Chemotherapy
107
Atezolizumab
98
Atezolizumab
Chemotherapy
Censored
Landmark
Arm A (atezo)
n=107
Arm B (chemo)
n=98
6-month PFS
(95% CI), %
59.8
(50.4, 69.2)
38.3
(28.5, 48.1)
12-month PFS
(95% CI), %
36.9
(27.0, 46.9)
21.6
(12.6, 30.6)
IMpower110: PFS in TC3/IC3 population
*Investigator assessed per RECIST 1.1; ‡Stratified; §Stratified log-rank; ¶For descriptive purposes
only Data cut-off: 10 September 2018
Spigel, et al. ESMO 2019 (Abs LBA78)
HR,‡ 0.63 (95% CI: 0.45, 0.88); P = 0.0070§¶
Median PFS, 8.1 mo
(95% CI: 6.8, 11.0)
Median PFS, 5.0 mo
(95% CI: 4.2, 5.7)
There was a clinically meaningful improvement
in PFS* in the atezolizumab arm
PFS was not formally tested in the TC3/IC3
population due to the hierarchical statistical plan
15. Median DOR
(range), mo
NE
(1.8+ to 29.3+)
6.7
(2.6 to 23.9+)
Arm B
0
10
20
30
40
50
60
Response
(%)
38.3%
28.6%
TC3 or IC3 WT
Arm A (atezo)
Arm B (chemo)
PR CR
Arm A
IMpower110: confirmed ORR (TC3 or IC3 population)
+, censored
Data cut-off: 10 September 2018
Spigel, et al. ESMO 2019 (Abs LBA78)
Arm A (atezo) Arm B (chemo)
TC2/3 or IC2/3 WT n=166 n=162
ORR (95% CI), %
30.7
(23.8, 38.3)
32.1
(25.0, 39.9)
Median DOR
(range), mo
NE
(1.8+ to 29.3+)
5.8
(2.6 to 23.9+)
TC1/2/3 or IC1/2/3 WT n=277 n=277
ORR (95% CI), %
29.2
(24.0, 35.0)
31.8
(26.3, 37.6)
Median DOR
(range), mo
NE
(1.8+ to 29.3+)
5.7
(2.4 to 23.9+)
Confirmed ORR was improved with Atezolizumab
in the TC3/IC3 population
16. IMpower110: updated safety profile
*Pooled atezolizumab monotherapy patients (across indications and therapy lines)
‡Grade 3–4 AE/immune-mediated AEs: number of patients whose highest grades of AE/immune-mediated AEs are 3 or 4
§Immune-mediated AEs (imAEs) were defined per a sponsor-specified list of terms, regardless of whether the events led to
systemic glucocorticoid, endocrine therapy, or other immunosuppressant use
±AData cut-off: 10 September, 2018
Follow-up: 13.7 months
Jassem, et al. ASCO 2020 (Abs e21623)
Adverse events Atezolizumab
N=286
Chemotherapy
N=263
Pooled atezolizumab
monotherapy
population*
N=3178
Grade 3–4 AEs‡ 86 (30.1) 138 (52.5) 1482 (46.6)
Related Grade 3–4 AEs‡ 37 (12.9) 116 (44.1) 496 (15.6)
Grade 5 AEs 11 (3.8) 11 (4.2) 119 (3.7)
Related Grade 5 AEs 0 1 (0.4) 11 (0.3)
AE leading to any treatment withdrawal 18 (6.3) 43 (16.3) 226 (7.1)
Immune-mediated AEs§ 115 (40.2) 44 (16.7) 1097 (34.5)
Grade 3–4 immune-mediated AEs‡§ 19 (6.6) 4 (1.5) 248 (7.8)
Immune-mediated AEs requiring
corticosteroids use
30 (10.5) 3 (1.1) 247 (7.8)
The atezolizumab arm and pooled atezolizumab monotherapy population demonstrated a
favourable safety profile compared with chemotherapy
17. Arm B (chemo)
n=263
Arm A (atezo)
n=286
Vomiting
Decreased neutrophil count
Hypothyroidism
Thrombocytopenia
Anaemia
Nausea
Neutropenia
Constipation
Increased blood creatinine
Leukopenia
Decreased platelet count
Pruritus
Increased AST
40% 30% 20% 10% 0 10% 20% 30% 40% 50%
50%
More
frequent
with
chemo
More
frequent
with
atezo
IMpower110: all-cause AEs (>5% difference
between arms)
AST, aspartate aminotransferase
Spigel, et al. ESMO 2019 (Abs LBA78)
18. IMpower110: summary
• Atezolizumab represents a promising 1L treatment option in patients with PD-L1–high
NSCLC
• IMpower110 is a positive study that demonstrated statistically significant and clinically
meaningful improvement of OS in the TC3 or IC3 WT population versus platinum-based
chemotherapy
(HR, 0.59 [95% CI: 0.40, 0.89]; P = 0.0106)
• In the TC3 or IC3 WT population, Atezolizumab showed meaningful improvement in PFS,
ORR and DOR versus chemotherapy
• The safety profile of Atezolizumab was consistent with prior observations; no new or
unexpected safety signals were identified
• Atezolizumab had a favourable safety profile compared with chemotherapy, and the safety
data were consistent with those from a pooled Atezolizumab monotherapy population
• Patients treated with Atezolizumab had a longer treatment exposure than patients treated
with chemotherapy
Spigel, et al. ESMO 2019 (Abs LBA78); Jassem, et al. ASCO 2020 (Abs e21623)
20. Until PD or
loss of clinical
benefit
Until PD
Atezolizumab
Atezolizumab
+
Bevacizumab
Bevacizumab
Until PD or
loss of clinical
benefit
Stage IV Non-Squamous
NSCLC
Chemotherapy naïve
Stratification factors:
• Sex
• PD-L1 IHC expression*
• Liver mets
N=1202
R
1:1:1
A: Atezolizumab +
Carboplatin +
Paclitaxel
C: Carboplatin +
Paclitaxel +
Bevacizumab
B: Atezolizumab +
Carboplatin +
Paclitaxel +
Bevacizumab
Maintenance
(No crossover permitted)
Non-squamous
IMpower150: phase III study of first-line atezolizumab plus
chemotherapy and bevacizumab in non-squamous NSCLC
*PD-L1 testing by SP142 IHC assay
NCCN guidelines version 6 2020; Planchard, et al. Ann Oncol 2018 (updated 18 Sept 2019)
NCT02366143; GO29436
Key clinical questions:
• Does the addition of atezolizumab to the SoC bevacizumab
+ paclitaxel + carboplatin add clinical benefit?
• Is there improved clinical benefit if bevacizumab is replaced
by atezolizumab?
Atezolizumab + bevacizumab + carboplatin + paclitaxel
and bevacizumab + carboplatin + paclitaxel are
category 1 NCCN and ESMO recommended systemic
therapies for advanced metastatic disease in NSCLC
Co-primary endpoints:
• Investigator-assessed PFS in ITT-WT and Teff-high WT
• OS in ITT-WT
21. Atezolizumab anti-cancer immunity is enhanced through
bevacizumab’s VEGF-mediated effects
1. Gabrilovich, et al. Nat Med 1996; 2. Oyama, et al. J Immunol 1998; 3. Goel, et al. Physiol Rev 2011
4. Motz, et al. Nat Med 2014; 5. Hodi, et al. Cancer Immunol Res 2014; 6. Wallin, et al. Nat Commun 2016
7. Gabrilovich and Nagaraj. Nat Rev Immunol 2009; 8. Roland, et al. PLoS One 2009
9. Facciabene, et al. Nature 2011; 10. Voron, et al. J Exp Med 2015; 11. Chen and Mellman. Immunity 2013
12. Hodge, et al. Int J Cancer 2013; 13. Herbst, et al. Nature 2014
Bevacizumab inhibits VEGF-mediated
suppression of dendritic cell maturation,
enabling efficient priming and
activation of T-cell responses1,2
Bevacizumab normalises the tumour
vasculature, resulting in an increased
infiltration of T cells into the tumour3-6
Bevacizumab decreases the
activity of MDSCs and Treg cells,
and enables reprogramming of
the tumour microenvironment6-10
Atezolizumab’s ability to restore anti-cancer immunity through
T cell-mediated cancer cell killing11,13 is further enhanced through
bevacizumab’s VEGF-mediated immunomodulatory effects
Chemotherapy-induced
immunogenic cell death can trigger
the release of tumour antigens11,12
22. Baseline characteristics were well balanced between
arms
*The Teff gene signature high cut-off ≥‒1.91 was used; ‡1 patient in Arm A had
unknown PD-L1 IHC expression; §One patient had EGFR exon 19 deletion and
also tested ALK positive per central lab
TC1/2/3 or IC1/2/3 = TC or IC ≥1% PD-L1+; TC0 and IC0 = TC and IC <1% PD-L1+
Data cut-off: 22 January 2018
Socinski, et al. ASCO 2018 (Abs 9002)
Baseline characteristics
Arm A:
atezo + CP
(N=402)
Arm B:
atezo + bev + CP
(N=400)
Arm C (control):
bev + CP
(N=400)
Median age (range), years 63 (32–85) 63 (31–89) 63 (31–90)
Sex, male, n (%) 241 (60) 240 (60) 239 (60)
ECOG PS, 0, n (%) 180 (45) 159 (40) 179 (45)
Tobacco use history, n (%)
Current smoker | Previous smoker
Never smoker
98 (24) | 227 (57)
77 (19)
90 (23) | 228 (57)
82 (21)
92 (23) | 231 (58)
77 (19)
Liver metastases, yes, n (%) 53 (13) 52 (13) 57 (14)
EGFR mutation, positive, n (%) 45 (11) 34§ (9) 45 (11)
ALK rearrangement, positive, n (%) 9 (2) 11 (3) 20 (5)
KRAS mutation, positive/tested, n (%) 36/124 (29) 47/106 (44) 38/115 (33)
Teff gene signature expression, high, n (%)* 177 (44) 166 (42) 148 (37)
PD-L1 expression, n (%)‡
TC1/2/3 or IC1/2/3
TC0 and IC0
213 (53)
188 (47)
209 (52)
191 (48)
195 (49)
205 (51)
There was an approximate 50:50 split between
PD-L1-positive and –negative patients
10% of patients had EGFR
mutations, and these
patients were balanced
across the three arms
14% of patients had liver
metastases at baseline,
which were a stratification
factor in IMpower150
23. Median follow-up 39.8 months (updated OS analysis)
OS analysis for Arm B vs Arm C was considered final at the second interim analysis: data are
shown for descriptive purposes only
Data cut-off: 13 September, 2019
Socinski, et al. AACR 2020 (Abs CT216)
Median, 19.5 mo
(95% CI: 17.0, 22.2)
Median, 14.7 mo
(95% CI: 12.9, 17.1)
Arm B: atezo + bev + CP
Arm C: bev + CP
HR=0.80 (95% CI: 0.67, 0.95)
P=0.01
Median follow-up: 39.8 mo
(Updated OS analysis)
There was a significant OS benefit with the addition of
atezolizumab in the ITT-WT (Arm B vs Arm C)
Landmark OS, %
Arm B:
atezo + bev + CP
(N=359)
Arm C:
bev + CP
(N=337)
12-month 67% 61%
18-month 53% 41%
24-month 43% 34%
The improvement in
median OS of 4.5 months
is clinically meaningful
24. ORR and DOR were improved in the ITT population
*Investigator-assessed, confirmed per RECIST v1.1
Data cut-off: 22 January 2018 Socinski, et al. ASCO 2018 (Abs 9002)
Arm A: atezo + CP
Arm B: atezo + bev + CP
Arm C: bev + CP
PR CR
0%
10%
20%
30%
40%
50%
60%
70%
80%
Arm A Arm B Arm C
ITT
PD-L1–High
TC3 or IC3
PD-L1–Low
TC1/2 or IC1/2
PD-L1–Negative
TC0 and IC0
Arm A Arm B Arm C Arm A Arm B Arm C Arm A Arm B Arm C
Objective
Response
Rate
*
(%)
Median DOR
(range), mo
8.3
(1.9–26.0)
11.5
(2.0–29.0)
6.0
(1.5–23.1)
12.2
(1.9–26.0)
22.1
(2.8–29.0)
7.0
(1.5–22.1)
8.3
(2.8–24.5)
10.4
(2.7–24.3)
6.9
(2.8–23.1)
7.6
(1.9–24.9)
8.2
(2.0–24.6)
5.5
(2.0–16.6)
40%
56%
41%
62%
69%
49%
44%
58%
41%
31%
51%
36%
A high proportion of patients
responded to treatment with
atezolizumab + bevacizumab + chemo
Median DOR:
Arm B 11.5 months
Arm C 6.0 months 24
25. OS benefit was observed across all PD-L1 subgroups in the
ITT-WT (Arm B vs Arm C)
*Unstratified HR.
Data cut-off: January 22, 2018
Socinski, et al. ASCO 2018 (Abs 9002)
HR*=0.82
(95% CI: 0.62, 1.08)
(Second interim
OS analysis)
17.1 mo
14.1 mo
PD-L1–Low
TC1/2 or IC1/2
HR*=0.80
(95% CI: 0.55, 1.15)
(Second interim
OS analysis)
16.4 mo 20.3 mo
HR*=0.70
(95% CI: 0.43, 1.13)
(Second interim
OS analysis)
15.0 mo
PD-L1–High
TC3 or IC3
25.2 mo
PD-L1–Negative
TC0 and IC0
PD-L1-high patients
derived the most benefit
Atezo+Bev+CP (n=71)
Bev+CP (n=65)
Atezo+Bev+CP (n=121)
Bev+CP (n=105)
Atezo+Bev+CP (n=167)
Bev+CP (n=172)
26. Efficacy in key subgroups
EGFR TKI
EGFR TKI
EGFR+ after EGFR TKIs
27. EGFR+ subgroups in IMpower150
*Includes exon 19 deletion and Leu858Arg mutations.
‡WT refers to patients without EGFR or ALK genetic alterations.
Subgroup N representative at CCOD: 13 Sept 2019, following additional source
documentation verification. Reck, et al. Lancet Respir Med 2019
27
EGFR mutation
(n=124)
Sensitising
EGFR mutation*
(n=91)
Sensitising EGFR
mutation and
prior TKI therapy
(n=78)
ITT-WT‡
(n=1,042)
EGFR mutation
or ALK
rearrangement
(n=160)
ITT population
(N=1,202)
28. Clinically meaningful PFS benefit was observed for Arm B vs
Arm C in patients with EGFR Mut+/ALK+ NSCLC
*Unstratified HR
Data cut-off: September 15, 2017
Kowanetz, et al. AACR 2018 (Abs CT076 - presented by Socinski)
Arm B: atezo + bev + CP (n=44)
Arm C: bev + CP (n=64)
HR*=0.59
(95% CI: 0.37, 0.94)
(Primary analysis)
Median, 6.1 mo
(95% CI: 5.7, 8.4)
Time (months)
Progression-Free
Survival
(%)
Median, 9.7 mo
(95% CI: 6.9, 15.2)
The PFS KM curves
separate at around
6 months
29. OS benefit in patients with sensitizing EGFR mutations
Minimum follow-up 32.4 months (updated OS analysis)
OS for Arm B versus C was considered final at the second interim analysis, updated data is for descriptive purposes
only
Data cut-off: 13 September 2019
Socinski et al. AACR 2020 (Abs CT216)
Median, 29.4 mo
(95% CI: 24.9, NE)
Median, 18.1 mo
(95% CI: 11.7, 27.8)
Median, 19.0 mo
(95% CI: 13.5, 28.5)
Median, 18.1 mo
(95% CI: 11.7, 27.8)
29
HR=0.60
(95% CI: 0.31, 1.14)
Minimum follow-up: 32.4 mo
(Updated OS analysis)
HR=1.00
(95% CI: 0.57, 1.74)
Minimum follow-up: 32.4 mo
(Updated OS analysis)
Arm B vs Arm C Arm A vs Arm C
No benefit was observed between
Arm A vs C
There was continued clear
separation of curves and OS benefit
with the addition of atezolizumab to
bevacizumab + chemotherapy
30. ORR and DOR were improved with bevacizumab + Atezolizumab
+ chemotherapy in patients with EGFR+ NSCLC
*Unstratified HR
Data cut-off: 22 January, 2018
Reck, et al. Lancet Respir Med 2019
71
42
0
20
40
60
80
ORR
(%)
Atezolizumab
+ bevacizumab
+ CP
(n=31)
Bevacizumab
+ CP
(n=23)
Median DOR, mo 11.1 4.7
n=24 n=18
ORR and DOR
ORR increased from 42% to 71%
with the addition of atezolizumab
to bevacizumab + chemotherapy
CR rate 6%
CR rate 0%
32. HR=0.41 (95% CI: 0.26, 0.62)
(Updated PFS analysis)
Clinically meaningful PFS was observed for Arm B vs Arm C
(ITT) in patients with liver metastasis at baseline
Unstratified HR
Data cut-off: January 22 2018
Reck et al. Lancet Respir Med 2019
Patients with liver metastases have
clinically meaningful survival benefit with
the IMpower150 regimen, despite liver
metastases being a negative prognostic
factor in NSCLC
6 months 12 months 18 months
Arm B (ABCP) 58.0% 34.0% 23.3%
Arm C (BCP) 37.8% 1.8% 1.8%
Landmark PFS
Median 5.4 mo
(95% CI 4.1–6.0)
Median 8.2 mo
(95% CI 5.7–10.3)
33. An OS benefit was observed in patients with liver metastases
when bevacizumab was added to atezolizumab
Data cut-off: 22 January, 2018
Socinski, et al. ASCO 2019 (Abs 9012)
Reck, et al. Lancet Respir Med 2019
No OS benefit was observed
when comparing Arm A
with Arm C
Liver metastases (ITT)
Arm B vs Arm C
Liver metastases (ITT)
Arm A vs Arm C
HR=0.52 (95% CI: 0.33, 0.82)
(Second interim OS analysis)
HR=0.87 (95% CI: 0.57, 1.32)
(Second interim OS analysis)
The KM curves separate early
and stay separated;
atezolizumab + bevacizumab
+ chemotherapy improves OS
6 months 12 months 18 months
Arm B (ABCP) 60.0% 40.7% 34.9%
Arm C (BCP) 35.9% 17.3% 11.5%
6 months 12 months 18 months
Arm B (ABCP) 40.0% 25.4% 14.3%
Arm C (BCP) 35.9% 17.3% 11.5%
The combination of both atezolizumab and
bevacizumab are important for the clinically relevant OS
benefit in patients with liver metastases
34. Addition of bevacizumab to atezolizumab + chemotherapy
improved ORR and DOR in patients with liver metastases
*Unstratified HR
Data cut-off: 22 January, 2018 Socinski, et al. ASCO 2019 (Abs 9012)
Reck, et al. Lancet Respir Med 2019
Atezolizumab +
bevacizumab + CP
(n=31)
Bevacizumab
+ CP
(n=23)
Median DOR, mo 10.7 4.6
DOR HR v
bevacizumab + CP
(95% CI)
0.39
(0.21–0.73)
–
60.8
41.1
0
20
40
60
80
ORR
(%)
ORR and DOR
n=51 n=56
mDOR was nearly doubled with addition of
bevacizumab to atezolizumab + chemotherapy in
patients with liver metastases
35. Efficacy in key subgroups:
Patients with
bulky disease
≥3rd quartile
<3rd quartile
An exploratory analysis from IMpower150 evaluated efficacy in
Arm B vs Arm C using two different measures of bulky disease
High disease burden
Low disease burden
≥median
<median
36. IMpower150: efficacy outcomes of high and low disease burden
subgroups defined by SLD and number of metastatic sites
Data cut-off: 13 September, 2019
Minimum follow-up 32.4 months
*Pts with baseline measurable disease. SLD, sum of the longest diameter
3rd quartile was 108mm, with ‘high’ defined as SLD ≥108mm and ‘low’ defined as <108mm
Median number of metastatic sites at baseline: the median number of sites was 2, with ‘high’
defined as ≥2 metastatic sites and ‘low’ defined as <2 metastatic sites
Jotte, et al. ASCO 2020 (Abs e21637)
High burden
(SLD ≥3rd quartile)
Low burden
(SLD <3rd quartile)
High burden
(no of met sites ≥median)
Low burden
(no of met sites <median)
Arm B
Atezo + bev
+ CP
(n=91)
Arm C
Bev
+ CP
(n=85)
Arm B
Atezo + bev +
CP
(n=266)
Arm C
Bev
+ CP
(n=252)
Arm B
Atezo + bev
+ CP
(n=210)
Arm C
Bev
+ CP
(n=190)
Arm B
Atezo + bev
+ CP
(n=149)
Arm C
Bev
+ CP
(n=148)
Median OS,
months
15.5 10.7 20.3 17.1 17.6 12.5 22.5 21.5
OS HR
(95% CI)
0.70
(0.5–0.97)
0.83
(0.68–1.02)
0.72
(0.58–0.90)
0.89
(0.67–1.17)
ORR, %* 62 41 53 40 57 40 53 40
These data further support the use of
atezolizumab + bevacizumab +
chemotherapy as a first-line option for
patients with a high disease burden
The clinical benefit from addition of atezolizumab to
bevacizumab + CP was observed in patients with and
without bulky disease, regardless of the approach used
to define ‘bulky’. This benefit was even more pronounced
in the high disease burden subgroups
37. Atezolizumab + bevacizumab + chemotherapy was well tolerated with a
safety profile consistent with the known safety profiles of each drug
*Related to any study treatment. ‡Including fatal haemorrhagic AEs: Arm A: 2; Arm B: 6; Arm C: 3. §Immune-related AEs were
defined using MedDRA Preferred Terms that included both diagnosed immune conditions and signs and symptoms potentially
representative of immune-related events, regardless of investigator-assessed causality. ¶In Arm A, 1 patient had grade 5 acute
hepatitis and 1 patient had grade 5 interstitial lung disease. Data cut-off: 22 January 2018
Socinski, et al. ASCO 2018 (Abs 9002)
Incidence, n (%)
Arm A:
atezo + CP
(n=400)
Arm B:
atezo + bev + CP
(n=393)
Arm C (control):
bev + CP
(n=394)
Median doses received (range), n
Atezolizumab
Bevacizumab
10 (1-43)
NA
12 (1-44)
10 (1-44)
NA
8 (1-38)
Treatment-related AE*
Grade 3-4
Grade 5‡
377 (94%)
172 (43%)
4 (1%)
370 (94%)
223 (57%)
11 (3%)
377 (96%)
191 (49%)
9 (2%)
Serious AE 157 (39%) 174 (44%) 135 (34%)
AE leading to withdrawal from any treatment 53 (13%) 133 (34%) 98 (25%)
Immune-related AEs§ in > 5 patients in any arm All grade Grade 3-4 All grade Grade 3-4 All grade Grade 3-4
Rash 119 (30%) 14 (4%) 117 (30%) 9 (2%) 53 (14%) 2 (1%)
Hepatitis¶
Laboratory abnormalities
42 (11%)
36 (9%)
12 (3%)
10 (3%)
54 (14%)
48 (12%)
20 (5%)
18 (5%)
29 (7%)
29 (7%)
3 (1%)
3 (1%)
Hypothyroidism 34 (9%) 1 (<1%) 56 (14%) 1 (<1%) 18 (5%) 0
Pneumonitis¶ 23 (6%) 8 (2%) 13 (3%) 6 (2%) 5 (1%) 2 (1%)
Hyperthyroidism 11 (3%) 0 16 (4%) 1 (<1%) 5 (1%) 0
Colitis 3 (1%) 2 (1%) 11 (3%) 7 (2%) 2 (1%) 2 (1%)
• The safety profiles of ABCP and ACP were similar to A, B and C+P individually; no new safety
signals were identified with the combinations
There was a higher
proportion of treatment-
related grade 3–5 AEs and
AEs of special interest in
Arm B; this was expected,
due to the additive effects of
four drugs instead of three
38. IMpower150: Conclusion
IMpower150 is a positive study in 1L non-squamous NSCLC, with statistically
significant and clinically meaningful improvement in both co-primary
endpoints of OS and PFS for the Atezo+Bev+CP arm vs. Bev+CP arm
Additional patient characteristics beyond PD-L1 expression may be considered
when making CIT treatment decisions for non-squamous NSCLC patients
Liver
metastases
EGFR
mutations
Clinical benefit was observed in key subgroups of patients with EGFR/ALK
genomic alterations and liver metastases at baseline, with the addition of
bevacizumab to atezolizumab + chemotherapy
Atezolizumab in combination with chemotherapy ± bevacizumab is well
tolerated and its safety profile is consistent with known safety risks
39. Summary
IMpower 150: Phase III multicentre, international, randomised, open-label, 3-arm trial in
chemotherapy-naïve patients with non-squamous mNSCLC (Atezolizumab + Bevacizumab +
carbo/pac vs Bevacizumab + carbo/pac)
Atezolizumab + Bevacizumab + carbo/pac is the first CIT combination to demonstrate
meaningful OS in EGFR+ patients and patients with liver metastases
Atezolizumab + Bevacizumab + carbo/pac nearly doubled PFS benefit at 12 months:
12-month PFS was 38% with Atezolizumab + Bevacizumab + carbo/pac vs 20% with Avastin +
carbo/pac alone
42. Rationale for combining Atezolizumab
with chemotherapy
1. Chen and Mellman. Immunity 2013; 2. Herbst, et al. Nature 2014
3. Hodge, et al. Int J Cancer 2013
Atezolizumab has the ability to
restore anti-cancer immunity by
preventing T-cell deactivation1,2
Atezolizumab
Chemotherapy-induced
immunogenic cell death can trigger
the release of tumour antigens1,3
Chemotherapy
The goal of CIT combinations is to create a more favourable environment
to maximise the potential of the immune system to eliminate cancer
43. IMpower130 trial design
*Patients with a sensitising EGFR mutation or ALK translocation must have experienced
progression (during or after treatment) or intolerance to treatment with one or more EGFR TKIs or
ALK inhibitors‡PD-L1 testing by SP142 IHC assay
Survival
follow-up
Atezolizumab
until PD or loss
of clinical benefit
Pemetrexed
until PD
Atezolizumab
Pemetrexed
or BSC
Stage IV non-squamous
NSCLC
Chemotherapy naïve*
ECOG PS 0–1
Stratification factors:
•Sex
•PD-L1 IHC expression‡
•Liver mets
ITT: N=723
ITT-WT: N=679
R
2:1
Arm A: atezolizumab
+ carboplatin +
nab-paclitaxel
(4–6 cycles)
Arm B: Carboplatin +
nab-paclitaxel
(4–6 cycles)
Maintenance
Non-squamous
Switch maintenance to
pemetrexed was permitted
in the control arm
Dosing:
Atezolizumab: 1,200mg q3w
Carboplatin: AUC 6 q3w
Nab-paclitaxel: 100mg/m2 on days 1, 8, 15 q3w
The use of nab-paclitaxel in IMpower130
provides an alternative, potential steroid-
sparing chemotherapy regimen
Crossover from Arm B to Arm A
was initially permitted; crossover
was not permitted following the
June 2016 protocol amendment
Despite the protocol amendment, 41% of patients
in the control arm crossed over to atezolizumab
on-study, with a total of 59% of patients in the
control arm receiving subsequent CIT
Co-primary endpoint: INV-assessed PFS in ITT-WT;
OS in ITT-WT
secondary endpoints: INV-assessed PFS and OS in ITT; INV-
assessed PFS and OS in PD-L1 selected populations (TC2/3
or IC2/3 and TC1/2/3 or IC1/2/3)
44. Baseline characteristics were generally well balanced
between arms (ITT-WT*)
Data are n (%); *32 patients in the atezo + CnP arm and 12 patients in the CnP arm had EGFR or ALK genomic
alterations and were not included in the ITT-WT population; ‡PD-L1-high (TC3 or IC3): patients with PD-L1 expression
in ≥50% of TC or ≥10% of IC; §PD-L1-low (TC1/2 or IC1/2): patients with PD-L1 expression in ≥1% and <50% of TC or
≥1% and <10% of IC; ¶PD-L1-negative (TC0 and IC0): patients with PD-L1 expression in <1% of TC and <1% of IC
Cappuzzo, et al. ESMO 2018 (Abs LBA53)
Atezo + CnP
(n=451)
CnP
(n=228)
Age group (years)
<65
65–74
75–84
≥85
227 (50.3%)
174 (38.6%)
48 (10.6%)
2 (0.4%)
114 (50.0%)
84 (36.8%)
29 (12.7%)
1 (0.4%)
Sex
Female
Male
185 (41.0%)
266 (59.0%)
94 (41.2%)
134 (58.8%)
Liver metastases at enrolment
Present
Not present
69 (15.3%)
382 (84.7%)
31 (13.6%)
197 (86.4%)
Bone metastases 126 (27.9%) 63 (27.6%)
Race
White
Black or African American
Asian
Multiple
Unknown
402 (89.1%)
17 (3.8%)
12 (2.7%)
1 (0.2%)
19 (4.2%)
210 (92.1%)
8 (3.5%)
3 (1.3%)
0
7 (3.1%)
Atezo + CnP
(n=451)
CnP
(n=228)
ECOG PS
0 189 (42.0%) 91 (39.9%)
Tobacco use history
Never
Current
Previous
48 (10.6%)
92 (20.4%)
311 (69.0%)
17 (7.5%)
51 (22.4%)
160 (70.2%)
Planned 4 vs 6 cycles
4 cycles
6 cycles
227 (50.3%)
224 (49.7%)
119 (52.2%)
109 (47.8%)
PD-L1 tumour expression
PD-L1-high‡
PD-L1-low§
PD-L1-negative¶
88 (19.5%)
128 (28.4%)
235 (52.1%)
42 (18.4%)
65 (28.5%)
121 (53.1%)
45. Median: 7.0 mo
(95% CI: 6.2, 7.3)
Median: 5.5 mo
(95% CI: 4.4, 5.9)
Progression
Free
Survival
(%)
HR=0.64
(95% CI: 0.54, 0.77)
P < 0.0001
Median follow-up: ~19 mo
PFS (%) 6 months 12 months
Atezo + CnP (n=451) 56.1% 29.1%
CnP (n=228) 42.5% 14.1%
Investigator-assessed PFS was significantly improved with
addition of Atezolizumab to carboplatin + nab-paclitaxel (ITT-WT)
Median follow-up: ~19 months
West et al. Lancet Oncol 2019
PFS was also significantly improved in the ITT population
Landmark 12-month PFS was
doubled with the addition of
atezolizumab to carboplatin
and nab-paclitaxel
46. Median: 18.6 mo
(95% CI: 16.0, 21.2)
Median: 13.9 mo
(95% CI: 12.0, 18.7)
Overall
Survival
(%)
HR=0.79
(95% CI: 0.64, 0.98)
P = 0.033
OS (%) 1 year 2 years
Atezo + CnP (n=451) 63.1% 39.6%
CnP (n=228) 55.5% 30.0%
OS was significantly improved with addition of
Atezolizumab to carboplatin + nab-paclitaxel (ITT-WT)
Median follow-up: ~19 months
West et al. Lancet Oncol 2019
OS was also significantly improved in the ITT population
OS is significantly improved in the
Atezo + CnP arm versus the CnP
arm, despite 59% of patients in the
control arm receiving subsequent
CIT (including 41% crossover
to atezolizumab)
47. West, et al. Lancet Oncol 2019
0.1 1 10
Population n (%) Atezo + CnP CnP HR (95% CI)
Female 279 (41.1) 21.4 12.8 0.66 (0.46, 0.93)
Male 400 (58.9) 16.0 14.2 0.87 (0.66, 1.15)
<65 years 341 (50.2) 19.2 16.6 0.79 (0.58, 1.08)
≥65 years 338 (49.8) 16.1 12.6 0.78 (0.58, 1.05)
ECOG PS*
0 280 (41.3) 20.8 19.7 0.85 (0.59, 1.22)
1 397 (58.6) 15.2 11.9 0.77 (0.58, 1.00)
2 1 (0.1) N/A N/A N/A (N/A, N/A)
Never smoker 65 (9.6) 28.2 19.5 0.55 (0.26, 1.19)
Current/previous smoker 614 (90.4) 18.1 13.9 0.81 (0.65, 1.02)
No liver mets at enrolment 579 (85.3) 21.1 15.2 0.73 (0.57, 0.92)
Liver mets at enrolment 100 (14.7) 10.0 8.8 1.04 (0.63, 1.72)
PD-L1-high (TC3 or IC3) 130 (19.1) 17.3 16.9 0.84 (0.51, 1.39)
PD-L1-low (TC1/2 or IC1/2) 193 (28.4) 23.7 15.9 0.70 (0.45, 1.08)
PD-L1-negative (TC0 and IC0) 356 (52.4) 15.2 12.0 0.81 (0.61, 1.08)
ITT-WT 679 (100) 18.6 13.9 0.79 (0.64, 0.98)
Favours atezo+CnP Favours CnP
Median OS (mo)
An OS benefit was observed across clinically relevant
subgroups in the ITT-WT population
Stratified HR for ITT-WT; unstratified HR for all other subgroups
*One patient had an unknown ECOG PS.
48. HR=0.98
(95% CI: 0.41, 2.31)
Overall
Survival
(%)
Median: 14.4 mo
Median: 10.0 mo
Progression
Free
Survival
(%)
Median: 7.0 mo
Median: 6.0 mo
HR=0.75
(95% CI: 0.36, 1.54)
OS
Investigator-assessed PFS
No PFS or OS benefit was observed over chemotherapy
alone in patients with EGFR/ALK+ NSCLC
Cappuzzo, et al. ESMO 2018 (Abs LBA53)
IMpower150 remains the only phase III study to
demonstrate clinical benefit of a CIT combination
regimen (atezolizumab in combination with bevacizumab
plus chemotherapy) in patients with EGFR/ALK+ NSCLC
Atezo+CnP (n=32)
CnP (n=12)
49. Atezo+CnP
(n=220)
CnP
(n=72)
Median DOR, mo (95% CI) 8.4 (6.9, 11.8) 6.1 (5.5, 7.9)
P value (stratified)* 0.0004
ORR and DOR were improved in Arm A versus
Arm B (ITT-WT)
The number of missing or unevaluable cases was 42 (9.4%) in the atezo + CnP arm and 27 (11.9%) in the CnP
arm
*For descriptive purposes only.
Cappuzzo, et al. ESMO 2018 (Abs LBA53)
49.2
31.9
2.5 1.3
46.8
30.5 30.4
38.1
11
18.1
0
10
20
30
40
50
60
Response
(%)
n=220 n=72 n=11 n=3 n=209 n=69 n=136 n=86 n=49 n=41
ORR CR PR SD PD
A higher proportion of patients
have a complete or partial
response in the experimental arm
compared with the control arm
50. Atezolizumab + carboplatin + nab-paclitaxel was well tolerated with a
safety profile consistent with the known safety profiles of each drug
Data are n (%) or median (range); safety data are included for the CnP arm for patients up until crossover
49/232 patients treated with CnP received pemetrexed switch maintenance
*Related to any treatment
Cappuzzo, et al. ESMO 2018 (Abs LBA53)
Atezo + CnP
(n=473)
CnP
(n=232)
Treatment duration, median (range), mo
Nab-paclitaxel
Carboplatin
Atezolizumab
Pemetrexed
2.8 (0–7)
2.3 (0–6)
6.9 (0–32)
–
2.7 (0–5)
2.3 (0–5)
–
3.5 (0–16)
All-cause AE, n (%)
Grade 3–4
Grade 5
471 (99.6%)
381 (80.5%)
25 (5.3%)
230 (99.1%)
164 (70.7%)
13 (5.6%)
Treatment-related AE, n (%)*
Grade 3–4
Grade 5
455 (96.2%)
346 (73.2%)
8 (1.7%)
215 (92.7%)
140 (60.3%)
1 (0.4%)
Serious AE, n (%)
Treatment-related serious AEa
240 (50.7%)
112 (23.7%)
88 (37.9%)
30 (12.9%)
Treatment-related AEs of special interest, n (%)
Grade 3–4
Grade 5
168 (35.5%)
24 (5.1%)
3 (0.6%)
34 (14.7%)
6 (2.6%)
0
AE leading to any treatment withdrawal, n (%) 125 (26.4%) 51 (22.0%)
AE leading to any dose interruption or modification, n (%) 402 (85.0%) 186 (80.2%)
There was a higher proportion of treatment-related
grade 3–5 AEs and AEs of special interest in the
Atezo+CnP arm, which is expected, due to the
additive effects of three drugs instead of two
51. Key conclusions IMpower 130
Atezo plus chemotherapy had a safety profile consistent with AEs associated with single-agent therapy;
no new safety signals were identified
IMpower130 demonstrated statistically significant and clinically relevant OS benefit when atezolizumab
was added to carboplatin + nab-paclitaxel, despite the high crossover rate
IMpower130 was a positive phase III study for atezolizumab in 1L NSCLC, providing an alternative
CIT + chemotherapy regimen for patients with chemotherapy-naïve NSCLC
An OS and PFS benefit was observed across key clinical subgroups, except in patients with EGFR/ALK+
NSCLC or patients with liver metastases, supporting use of the IMpower150 regimen in those patients
IMpower130 demonstrated a PFS benefit and a higher ORR when atezolizumab was added to
carboplatin + nab-paclitaxel
52. For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only.
Full prescribing information available on request. For scientific information on Roche Medicinal Product please write to india.medinfo@roche.com
For all Adverse Events/Special Situation Reports with Roche Medicinal Product please report the same to india.drugssafety@roche.com within
one business day/24 hours. This promotional input is not valid after 14/12/2022
Marketed in India by:
Roche Products (India) Pvt. Ltd.
146-B, 166 A, Unit No. 7, 8, 9, 8th Floor, R City Office, R City Mall, Lal Bahadur Shastri Marg, Ghatkopar, Mumbai - 400 086
Maharashtra; Tel No. +91 22 50457300; Fax No. +91 22 50457301
M-IN-00001050
ABRIDGED PRESCRIBING INFORMATION
(Tecentriq ®) SUMMARY OF PRESCRIBING INFORMATION: Generic Name: Atezolizumab Injection, Brand Name: Tecentriq®. Composition: Active ingredient: Atezolizumab.
Tecentriq is supplied as a single-use vial containing preservative-free, colorless to slightly yellow solution, at an active ingredient concentration of 60 mg/mL as follows:14 mL vial containing a total of 840 mg Atezolizumab 20 mL vial containing a total of 1200 mg Atezolizumab. Indications:
Tecentriq® is indicated for- Urothelial carcinoma (UC) Tecentriq is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma after prior chemotherapy or who are considered cisplatin ineligible. Non-small cell lung cancer- Tecentriq is also indicated
for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. Tecentriq in combination with bevacizumab, paclitaxel and carboplatin, is indicated for the first-line treatment of adult patients with metastatic non-squamous non-
small cell lung cancer (NSCLC). In patients with EGFR, mutant or ALK-positive NSCLC, Tecentriq, in combination with bevacizumab, paclitaxel and carboplatin, is indicated only after failure of appropriate targeted therapies. Atezolizumab in combination with nab-paclitaxel and carboplatin,
is indicated for first-line treatment of patients with metastatic non-squamous NSCLC who do not have EGFR or ALK genomic tumor aberrations. Atezolizumab as monotherapy for the first line treatment of patients of metastatic NSCLC whose tumors have a PD L1 expression > 50% tumor
cells or > 10% tumor infiltrating immune cells and who do not have EGFR or ALK genomic tumor aberrations. Small cell lung cancer Tecentriq, in combination with carboplatin and etoposide, is indicated for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-
SCLC).Triple-negative breast cancer Tecentriq, in combination with nab-paclitaxel, is indicated for the treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumor have PD-L1 expression ≥1%, and who have not received prior
chemotherapy for metastatic disease. Hepatocellular carcinoma Atezolizumab, in combination with Bevacizumab, is indicated for the treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy.Type of dosage form:
Tecentriq® is available in single use vials as Concentrate for solution for infusion. Dosage and Administration: Tecentriq must be administered as an intravenous infusion under the supervision of a qualified healthcare professional. Do not administer as an IV push or bolus. The initial
dose of Tecentriq must be administered over 60 minutes. If the first infusion is tolerated all subsequent infusions may be administered over 30 minutes. The recommended dose of Tecentriq in monotherapy or combination therapy:840 mg administered by IV infusion every 2 weeks, or 1200
mg administered by IV infusion every 3 weeks Tecentriq monotherapy 2L NSCLC, 1L NSCLC, 2L UC & 1L UC in Cisplatin ineligible patients Tecentriq combination therapy 1L non-squamous NSCLC:Tecentriq in combination with bevacizumab, paclitaxel, and carboplatin:During the
induction phase, Tecentriq is administered according to its dosing schedules by intravenous (IV) infusion and bevacizumab, paclitaxel and carboplatin are administered every 3 weeks for four or six cycles. The induction phase is followed by a maintenance phase without chemotherapy in
which Tecentriq is administered according to its dosing schedules by IV infusion and bevacizumab is administered every 3 weeks. Tecentriq in combination with nab-paclitaxel and carboplatin:During the induction phase, the recommended dose of Tecentriq is 1200 mg administered by IV
infusion, followed by nab-paclitaxel and carboplatin every 3 weeks for four or six cycles. For each 21-day cycle, Tecentriq, nab-paclitaxel and carboplatin is administered on day 1. In addition, nab-paclitaxel is administered on days 8 and 15. The induction phase is followed by a
maintenance phase without chemotherapy in which 1200 mg Tecentriq is administered by IV infusion every 3 weeks.1L ES-SCLC: Tecentriq in combination with carboplatin and etoposide. During the induction phase, Tecentriq is administered according to its dosing schedules by IV
infusion and carboplatin and etoposide are administered by IV infusion every three weeks for four cycles. Carboplatin and etoposide are administered on day 1 of each cycle, and etoposide is also administered on days 2 and 3. The induction phase is followed by a maintenance phase
without chemotherapy in which Tecentriq is administered according to its dosing schedules by IV infusion. 1L TNBC: Tecentriq in combination with nab-paclitaxel: The recommended dose of Tecentriq is 840 mg administered by IV infusion, followed by 100 mg/m2 nab-paclitaxel. For each
28-day cycle Tecentriq is administered on days 1 and 15, and nab-paclitaxel is administered on days 1, 8 and 15. HCC: Tecentriq in combination with bevacizumab. Tecentriq is administered according to its dosing schedules by IV infusion, and bevacizumab 15 mg/kg is administered every
3 weeks. Duration of Treatment: Patients are treated with Tecentriq until disease progression or unacceptable toxicity in UC, NSCLC & ES-SCLC and patients are treated until disease progression or unacceptable toxicity in 1L TNBC.Contraindications: Tecentriq is contraindicated in
patients with a known hypersensitivity to Atezolizumab or any of the excipients. Warnings and Precautions: Immune-mediated pneumonitis: Cases of pneumonitis, including fatal cases, have been observed in clinical trials with Tecentriq. Treatment with Tecentriq should be permanently
discontinued for Grade 3 or 4 pneumonitis. Immune-mediated hepatitis: Cases of hepatitis, some leading to fatal outcomes, have been observed in clinical trials with Tecentriq. Treatment with Tecentriq should be permanently discontinued for Grade 3 or Grade 4 events. Immune-
mediated colitis: Cases of diarrhea or colitis have been observed in clinical trials with Tecentriq. Treatment with Tecentriq should be permanently discontinued for Grade 4 diarrhea or colitis. Immune-mediated endocrinopathies: Hypothyroidism, hyperthyroidism, adrenal insufficiency
and type 1 diabetes mellitus, including diabetic ketoacidosis, have been observed in clinical trials with Tecentriq. For Grade 4 Hypophysitis, treatment with Tecentriq should be permanently discontinued. Immune-mediated meningoencephalitis: Meningoencephalitis has been observed in
clinical trials with Tecentriq. Permanently discontinue for all grades of meningoencephalitis. Immune-mediated neuropathies: Myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome, which may be life threatening, were observed in patients receiving Tecentriq. Permanently
discontinue Tecentriq for all grades of immune mediated neuropathies. Immune-mediated pancreatitis: Pancreatitis, including increases in serum amylase and lipase levels, has been observed in clinical trials with Tecentriq. Treatment with Tecentriq should be permanently discontinued
for Grade 4, or any grade of recurrent pancreatitis. Immune-mediated myocarditis: Myocarditis has been observed in clinical trials with Tecentriq. Tecentriq should permanently discontinued for Grade 3 or 4 myocarditis. Immune-mediated myositis: Cases of myositis, including fatal
cases, have been observed in clinical trials with Tecentriq. Treatment with Tecentriq should be permanently discontinued for Grade 3 recurrent myositis or Grade 4 events. Immune-mediated nephritis: Nephritis has been observed in clinical trials with Tecentriq. Treatment with Tecentriq
should be permanently discontinued for Grade 3 or 4 nephritis. Infusion related reactions: Infusion related reactions (IRRs) have been observed in clinical trials with Tecentriq. Tecentriq should be permanently discontinued in patients with Grade 3 or 4 infusion related reactions.Immune-
mediated severe cutaneous adverse reactions: Immune-mediated severe cutaneous adverse reactions (SCARs), including cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients receiving Tecentriq. Patients should be monitored
for suspected severe skin reactions and other causes should be excluded. Tecentriq should be permanently discontinued for Grade 4 skin reactions, and corticosteroids should be administered. For confirmed SJS or TEN, Tecentriq should be permanently discontinued. Special populations:
Patients with autoimmune disease were excluded from clinical trials with Tecentriq. In the absence of data, Tecentriq should be used with caution in patients with autoimmune disease, after assessment of the potential risk-benefit. Embryofetal toxicity: Based on the mechanism of action,
the use of Tecentriq may cause fetal harm. Animal studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to increased risk of immune-related rejection of the developing fetus resulting in fetal death. Pregnant women should be advised of the potential risk to the
fetus. Women of childbearing potential should be advised to use highly effective contraception during treatment with Tecentriq and for 5 months after the last dose. Disease Specific precautions: Use of Atezolizumab in combination with bevacizumab, paclitaxel and carboplatin in
metastatic non-squamous non-small cell lung cancer Physicians should carefully consider the combined risks of the four-drug regimen of atezolizumab bevacizumab, paclitaxel and carboplatin before initiating treatment. Use of atezolizumab in combination with nab-paclitaxel in metastatic
triple negative breast cancer: Neutropenia and peripheral neuropathies occurring during treatment with Atezolizumab and nabpaclitaxel may be reversible with interruptions of nab-paclitaxel. Physicians should consult the nab paclitaxel summary of product characteristics (SmPC) for
specific precautions and contraindications of this medicine. Patients excluded from clinical trials: Patients with the following condition were excluded from clinical trials: a history of autoimmune disease, history of pneumonitis, active brain metastasis, HIV, hepatitis B or hepatitis C infection,
significant cardiovascular disease and patients with inadequate hematologic and end-organ function. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment; systemic immune stimulatory agents within 4 weeks or systemic immunosuppressive medicinal
products within 2 weeks prior to study entry were excluded from clinical trial. Use in Special population:Fertility: Based on animal studies, Tecentriq may impair fertility in females of reproductive potential while receiving treatment. Contraception: Female patients of childbearing potential
should use highly effective contraception and take active measures to avoid pregnancy while undergoing Tecentriq treatment and for at least 5 months after the last dose. Pregnancy: There are no clinical studies of Tecentriq in pregnant women. Tecentriq is not recommended during
pregnancy unless the potential benefit for the mother outweighs the potential risk to the fetus. Labor and Delivery: The use of Tecentriq during labor and delivery has not been established. Lactation: There is no information regarding the presence of atezolizumab in human milk, the effects
on the breastfed infant, or the effects on milk production. As human IgG is excreted in human milk, the potential for absorption and harm to the infant is unknown. Because of the potential for serious adverse reactions in breastfed infants from Tecentriq, advise women not to breastfeed
during treatment and for at least 5 months after the last dose. Pediatric use: Tecentriq is not approved for use in patients under the age of 18 years. The safety and efficacy of Tecentriq in this population has not been established. Tecentriq did not demonstrate clinical benefit in pediatric
patients in a clinical trial. Geriatric use: No overall differences in safety or efficacy were observed between patients ≥ 65 years of age and younger patients. Postmarketing Experience: Lung infection, Immunodeficiency, Blood sugar increased, chest infection, Pneumonitis, Platelet count
low, Neutropenia, Hypothyroidism, Bedridden, Hip facture. Undesirable Effects: This is not the complete list. The very commonly reported Adverse Events (AEs) with Tecentriq in monotherapy includes fatigue, decreased appetite, cough, nausea, dyspnea, , diarrhea, pyrexia, vomiting,
arthralgia, Musculoskeletal pain, back pain, urinary tract infection, asthenia, pruritus, rash, headache and in case of combination therapy it includes anemia, neutropenia, thrombocytopenia, leukopenia, hypothyroidism, constipation, peripheral oedema, lung infection, peripheral neuropathy,
nasopharyngitis, alopecia, hypertension. No new adverse drug reactions have been identified from post marketing experience. Interactions with other medicinal products and other forms of interaction: No formal pharmacokinetic drug-drug interaction studies have been conducted
with atezolizumab. Since atezolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected. Overdose: There is no information on overdose with Tecentriq. Storage: Vials: - Store in a refrigerator at 2°C - 8°C. Keep vial in the outer carton in
order to protect from light. DO NOT FREEZE. DO NOT SHAKE. This medicine should not be used after the Expiry Date shown on the pack. The diluted solution for infusion should be used immediately. If the solution is not used immediately, it can be stored for up to 30 days at 2°C-8°C, or
24 hours at ambient temperature (≤ 25°C) if prepared under aseptic conditions. This medicinal product must not be mixed with other medicinal products. Shelf-life: 3 Years for Atezolizumab Injection 1200mg/20ml and 2 Years for Atezolizumab Injection 840mg/14ml Please read full
prescribing information before usage. Details of Permission or License Number with date:IMP-063/2017 dated 31 March 2017 [1200mg/20ml] and dated 27 Sept 2019 [840mg/14ml].Date of Revision: Current at December 2021, Version 20.0