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
- The addition of selective internal radiation therapy (SIRT) to sorafenib (SOR) did not significantly improve overall survival compared to SOR alone in patients with advanced hepatocellular carcinoma based on two randomized controlled trials.
- Subgroup analyses found potential clinical benefits for younger patients, those with non-alcoholic disease etiology, and those without cirrhosis.
- Regorafenib, a multi-kinase inhibitor, significantly improved progression-free survival, overall survival, and disease control compared to placebo in patients with hepatocellular carcinoma progressing on sorafenib.
- Lenvatinib, an oral multi-kinase inhibitor, demonstrated non-inferior
Optimal treatment sequence left side ras wt - case based (1)madurai
1. The document discusses optimal treatment sequence for left side RAS wild-type and BRAF wild-type metastatic colorectal cancer (mCRC).
2. It describes four groups of patients with metastatic disease based on resectability and provides treatment goals for each. Most patients initially present with unresectable disease.
3. Factors that influence first-line treatment choices for mCRC include biomarker status, tumor location, treatment sequence, and patient characteristics. Molecular testing for RAS and BRAF is recommended to guide treatment decisions.
Biomarkers in head and neck cancers final ajeetAjeet Gandhi
This document provides an overview of biomarkers in head and neck cancers. It discusses how biomarkers can be used for early diagnosis, predicting response to therapy, and identifying therapeutic targets. Key points include:
- Biomarkers like HPV status, ERCC1, and beta-tubulin isoform III may help predict response to chemotherapy and radiation. HPV+ tumors have a better prognosis.
- The EGFR pathway is commonly dysregulated in head and neck cancers but targeting it has had limited success due to resistance mechanisms. EGFRvIII mutations may reduce sensitivity to cetuximab.
- Ongoing research explores using biomarkers to guide more personalized treatment, such as reducing therapy for HPV+ tumors or targeting pathways
The document summarizes highlights from the 11-ICML Lugano conference in 2011, including:
1) Studies showing the impact of the tumor microenvironment in lymphoma prognosis and the predictive value of increased macrophages in Hodgkin's lymphoma biopsies.
2) High response rates to antiviral treatment in patients with indolent B-cell lymphoma associated with HCV infection.
3) A PET-based approach can effectively guide treatment for limited-stage diffuse large B-cell lymphoma.
4) R-CHOP induction followed by rituximab maintenance improves survival over R-FC induction for elderly patients with mantle cell lymphoma.
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
- The addition of selective internal radiation therapy (SIRT) to sorafenib (SOR) did not significantly improve overall survival compared to SOR alone in patients with advanced hepatocellular carcinoma based on two randomized controlled trials.
- Subgroup analyses found potential clinical benefits for younger patients, those with non-alcoholic disease etiology, and those without cirrhosis.
- Regorafenib, a multi-kinase inhibitor, significantly improved progression-free survival, overall survival, and disease control compared to placebo in patients with hepatocellular carcinoma progressing on sorafenib.
- Lenvatinib, an oral multi-kinase inhibitor, demonstrated non-inferior
Optimal treatment sequence left side ras wt - case based (1)madurai
1. The document discusses optimal treatment sequence for left side RAS wild-type and BRAF wild-type metastatic colorectal cancer (mCRC).
2. It describes four groups of patients with metastatic disease based on resectability and provides treatment goals for each. Most patients initially present with unresectable disease.
3. Factors that influence first-line treatment choices for mCRC include biomarker status, tumor location, treatment sequence, and patient characteristics. Molecular testing for RAS and BRAF is recommended to guide treatment decisions.
Biomarkers in head and neck cancers final ajeetAjeet Gandhi
This document provides an overview of biomarkers in head and neck cancers. It discusses how biomarkers can be used for early diagnosis, predicting response to therapy, and identifying therapeutic targets. Key points include:
- Biomarkers like HPV status, ERCC1, and beta-tubulin isoform III may help predict response to chemotherapy and radiation. HPV+ tumors have a better prognosis.
- The EGFR pathway is commonly dysregulated in head and neck cancers but targeting it has had limited success due to resistance mechanisms. EGFRvIII mutations may reduce sensitivity to cetuximab.
- Ongoing research explores using biomarkers to guide more personalized treatment, such as reducing therapy for HPV+ tumors or targeting pathways
The document summarizes highlights from the 11-ICML Lugano conference in 2011, including:
1) Studies showing the impact of the tumor microenvironment in lymphoma prognosis and the predictive value of increased macrophages in Hodgkin's lymphoma biopsies.
2) High response rates to antiviral treatment in patients with indolent B-cell lymphoma associated with HCV infection.
3) A PET-based approach can effectively guide treatment for limited-stage diffuse large B-cell lymphoma.
4) R-CHOP induction followed by rituximab maintenance improves survival over R-FC induction for elderly patients with mantle cell lymphoma.
This document discusses treatment approaches for locally advanced non-small cell lung cancer (NSCLC). It presents a case of stage IIIB NSCLC and reviews the history and evolution of combined modality therapy using chemotherapy and radiotherapy. Concurrent chemoradiotherapy is now the standard of care and research focuses on optimizing radiotherapy dose/fractionation and integrating targeted therapies and prophylactic cranial irradiation to further improve outcomes.
1) The document discusses several studies presented at the ASCO 2020 conference regarding prostate cancer treatment updates. These include studies on chemo-hormonal therapy, androgen signaling inhibitors, and immunotherapy combinations.
2) A key study found that combining pembrolizumab and enzalutamide showed activity in patients with metastatic castration-resistant prostate cancer whose disease had progressed on enzalutamide, with an objective response rate of 12% and durable disease control.
3) Additional results from the conference included findings on predictive biomarkers, outcomes based on site of metastasis, and safety data from combination immunotherapy and targeted therapy trials for advanced prostate cancer.
RR-17%
mPFS-4.5 mon
mOS-9.2 mon
Phase III trial
Rec/met HNSCC
N=326
Mtx vs Mtx+BV
No benefit
[1] The document discusses targeted therapies for head and neck squamous cell carcinoma (HNSCC).
[2] It summarizes genetic alterations commonly seen in HNSCC and targeted agents used to treat HNSCC including EGFR inhibitors like cetuximab, IGF inhibitors, VEGF receptor inhibitors, and other non-receptor targets.
[3] The document analyzes clinical trials of cetuximab, panitumumab
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
The document summarizes key information about prostate cancer including incidence, mortality rates, clinical stages, risk groups for localized prostate cancer, treatment options for advanced disease including hormone therapy and chemotherapy, and results from clinical trials of chemotherapy agents like docetaxel and cabazitaxel.
Multimodality Treatment Of Stage Iii Nsclcfondas vakalis
1) Multimodality treatment including chemotherapy and radiotherapy has improved outcomes for stage III non-small cell lung cancer (NSCLC) over the past decade, increasing median survival by 5 months and 1-2 year survival by 10%.
2) Induction chemotherapy with a platinum agent and third-generation drug for 2-3 cycles followed by radiotherapy remains a good standard treatment for fit patients.
3) Concurrent chemoradiotherapy and combined modality approaches may offer further benefits but require more evidence, as they present increased toxicity risks that need to be weighed against uncertain survival gains.
Dasatinib is an effective first-line treatment for chronic myeloid leukemia (CML) based on results from the DASISION trial. The trial showed that dasatinib induced higher and faster rates of complete cytogenetic response and major molecular response compared to imatinib. At 5 years of follow-up, dasatinib maintained superior rates of molecular responses including deeper responses below 0.1% BCR-ABL1. Dasatinib therefore provides improved long-term outcomes for patients with newly diagnosed CML compared to standard imatinib treatment.
Apalutamide is a drug developed to treat non-metastatic castration-resistant prostate cancer. It works as a competitive antagonist of the androgen receptor by binding to it more efficiently than other drugs and preventing the receptor's nuclear localization. Clinical trials found apalutamide to be well tolerated and resulted in significant reductions in PSA levels in patients, demonstrating its robust anti-tumor activity for this cancer type.
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.
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.
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.
Immunotherapy maintenence for advanced urothelial cancerChandan K Das
- JAVELIN Bladder 100 was a phase 3 trial investigating avelumab maintenance therapy after platinum-based chemotherapy in patients with advanced urothelial carcinoma.
- The trial found avelumab maintenance significantly improved overall survival compared to best supportive care alone, with a 31% reduction in risk of death. Progression-free survival was also significantly improved.
- Subgroup analyses found overall survival benefits were consistent across all patient subgroups, including those with PD-L1-negative tumors. Response rates were also higher with avelumab maintenance.
- The safety profile of avelumab was manageable, with most treatment-related adverse events being grade 1-2 in severity and no new safety signals
This document summarizes new adjuvant treatment strategies for early-stage HER2-positive breast cancer. It discusses trials showing improved disease-free survival when adding trastuzumab to chemotherapy as adjuvant therapy. More recent trials show additional benefits from combining trastuzumab with pertuzumab or using neratinib after initial trastuzumab therapy. The APHINITY trial found that adding pertuzumab to trastuzumab and chemotherapy significantly reduced the risk of invasive disease recurrence compared to placebo, trastuzumab and chemotherapy in the interim analysis. Benefits were greater in patients with node-positive disease or hormone receptor-negative breast cancer.
This document summarizes the key points from a presentation on recent cancer research:
1. Several studies presented findings on improving outcomes for prostate cancer, glioblastoma, rectal cancer, and other cancers through optimized use of radiation therapy and chemotherapy.
2. One study found long-term androgen deprivation therapy improved outcomes more than short-term therapy for prostate cancer. Another found radiation improved survival for node-positive prostate cancer.
3. For glioblastoma, a study identified molecular subgroups with more favorable prognosis, while another found improved outcomes with dose-escalated radiation and temozolomide.
4. For rectal cancer, studies explored organ-sparing approaches and found hypofraction
This document summarizes clinical trial data for several drugs tested in advanced hepatocellular carcinoma (HCC) after sorafenib failure. It shows that regorafenib, cabozantinib, and ramucirumab each provided a median overall survival benefit of 1-3 months compared to placebo. Regorafenib had a median OS of 10.6 months versus 7.8 months for placebo. Cabozantinib had a median OS of 10.2 months versus 8 months for placebo. Ramucirumab plus BSC had a median OS of 8.5 months versus 7.3 months for placebo plus BSC. Lenvatinib was found to be non-inferior
The document summarizes several studies presented at the 2008 Gastrointestinal Cancers Symposium. The PACCE trial found that adding panitumumab to oxaliplatin or irinotecan chemotherapy did not improve outcomes and increased toxicity. The FFCD trial found higher response rates with 5-FU/irinotecan vs 5-FU alone in elderly patients with colorectal cancer. The X-ACT trial showed a trend toward improved survival with capecitabine vs 5-FU/LV as adjuvant therapy. Studies also suggested intermittent oxaliplatin dosing may improve outcomes and that KRAS mutation status predicts response to anti-EGFR antibodies like panitumumab.
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.
This document summarizes recent developments in the treatment of immune thrombocytopenia (ITP). It discusses new evidence on treatments for refractory ITP including rituximab, thrombopoietin receptor agonists (TPO-RAs), and long-term use of eltrombopag. A randomized controlled trial found that rituximab did not significantly reduce long-term treatment failure compared to placebo in previously steroid-treated ITP patients. Long-term use of eltrombopag for up to 3 years was found to be generally safe and effective at maintaining platelet counts. The document concludes that large, randomized studies are still needed to better understand new ITP treatment options and balancing risks versus benefits requires consideration
This document summarizes key findings from the SPARTAN clinical trial evaluating the efficacy of apalutamide for the treatment of non-metastatic castration-resistant prostate cancer. The study found that apalutamide significantly reduced the risk of distant metastasis or death by 72% compared to placebo. Apalutamide also improved progression-free survival, time to symptomatic progression, and delayed the time to initiation of cytotoxic chemotherapy. The most common adverse events with apalutamide were fatigue, hypertension, and rash.
This case study examines the use of cetuximab-based chemotherapy for the re-treatment of patients with metastatic colorectal cancer who had previously responded to cetuximab treatment but experienced disease progression after stopping treatment. The study aims to evaluate the overall response and safety of re-treating these patients with cetuximab-containing chemotherapy. It describes the study design, inclusion/exclusion criteria, experimental and control treatments, and primary/secondary outcome measures that will be assessed over a 2-year period.
This document summarizes the use of PET-CT in staging and assessing treatment response in Hodgkin's lymphoma. It discusses that PET-CT is an important tool for initial staging, assessing response to chemotherapy, and prognostic indicator when done after partial chemotherapy. The sensitivity and specificity of PET-CT is higher than CT alone for detecting nodal and organ involvement. PET-CT may avoid the need for bone marrow biopsy in some cases. Interim PET imaging helps distinguish residual mass as viable tumor or necrosis/fibrosis. The document also reviews chemotherapy regimens like ABVD, BEACOPP and Stanford V in early and advanced Hodgkin's lymphoma.
This document discusses treatment approaches for locally advanced non-small cell lung cancer (NSCLC). It presents a case of stage IIIB NSCLC and reviews the history and evolution of combined modality therapy using chemotherapy and radiotherapy. Concurrent chemoradiotherapy is now the standard of care and research focuses on optimizing radiotherapy dose/fractionation and integrating targeted therapies and prophylactic cranial irradiation to further improve outcomes.
1) The document discusses several studies presented at the ASCO 2020 conference regarding prostate cancer treatment updates. These include studies on chemo-hormonal therapy, androgen signaling inhibitors, and immunotherapy combinations.
2) A key study found that combining pembrolizumab and enzalutamide showed activity in patients with metastatic castration-resistant prostate cancer whose disease had progressed on enzalutamide, with an objective response rate of 12% and durable disease control.
3) Additional results from the conference included findings on predictive biomarkers, outcomes based on site of metastasis, and safety data from combination immunotherapy and targeted therapy trials for advanced prostate cancer.
RR-17%
mPFS-4.5 mon
mOS-9.2 mon
Phase III trial
Rec/met HNSCC
N=326
Mtx vs Mtx+BV
No benefit
[1] The document discusses targeted therapies for head and neck squamous cell carcinoma (HNSCC).
[2] It summarizes genetic alterations commonly seen in HNSCC and targeted agents used to treat HNSCC including EGFR inhibitors like cetuximab, IGF inhibitors, VEGF receptor inhibitors, and other non-receptor targets.
[3] The document analyzes clinical trials of cetuximab, panitumumab
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
The document summarizes key information about prostate cancer including incidence, mortality rates, clinical stages, risk groups for localized prostate cancer, treatment options for advanced disease including hormone therapy and chemotherapy, and results from clinical trials of chemotherapy agents like docetaxel and cabazitaxel.
Multimodality Treatment Of Stage Iii Nsclcfondas vakalis
1) Multimodality treatment including chemotherapy and radiotherapy has improved outcomes for stage III non-small cell lung cancer (NSCLC) over the past decade, increasing median survival by 5 months and 1-2 year survival by 10%.
2) Induction chemotherapy with a platinum agent and third-generation drug for 2-3 cycles followed by radiotherapy remains a good standard treatment for fit patients.
3) Concurrent chemoradiotherapy and combined modality approaches may offer further benefits but require more evidence, as they present increased toxicity risks that need to be weighed against uncertain survival gains.
Dasatinib is an effective first-line treatment for chronic myeloid leukemia (CML) based on results from the DASISION trial. The trial showed that dasatinib induced higher and faster rates of complete cytogenetic response and major molecular response compared to imatinib. At 5 years of follow-up, dasatinib maintained superior rates of molecular responses including deeper responses below 0.1% BCR-ABL1. Dasatinib therefore provides improved long-term outcomes for patients with newly diagnosed CML compared to standard imatinib treatment.
Apalutamide is a drug developed to treat non-metastatic castration-resistant prostate cancer. It works as a competitive antagonist of the androgen receptor by binding to it more efficiently than other drugs and preventing the receptor's nuclear localization. Clinical trials found apalutamide to be well tolerated and resulted in significant reductions in PSA levels in patients, demonstrating its robust anti-tumor activity for this cancer type.
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.
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.
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.
Immunotherapy maintenence for advanced urothelial cancerChandan K Das
- JAVELIN Bladder 100 was a phase 3 trial investigating avelumab maintenance therapy after platinum-based chemotherapy in patients with advanced urothelial carcinoma.
- The trial found avelumab maintenance significantly improved overall survival compared to best supportive care alone, with a 31% reduction in risk of death. Progression-free survival was also significantly improved.
- Subgroup analyses found overall survival benefits were consistent across all patient subgroups, including those with PD-L1-negative tumors. Response rates were also higher with avelumab maintenance.
- The safety profile of avelumab was manageable, with most treatment-related adverse events being grade 1-2 in severity and no new safety signals
This document summarizes new adjuvant treatment strategies for early-stage HER2-positive breast cancer. It discusses trials showing improved disease-free survival when adding trastuzumab to chemotherapy as adjuvant therapy. More recent trials show additional benefits from combining trastuzumab with pertuzumab or using neratinib after initial trastuzumab therapy. The APHINITY trial found that adding pertuzumab to trastuzumab and chemotherapy significantly reduced the risk of invasive disease recurrence compared to placebo, trastuzumab and chemotherapy in the interim analysis. Benefits were greater in patients with node-positive disease or hormone receptor-negative breast cancer.
This document summarizes the key points from a presentation on recent cancer research:
1. Several studies presented findings on improving outcomes for prostate cancer, glioblastoma, rectal cancer, and other cancers through optimized use of radiation therapy and chemotherapy.
2. One study found long-term androgen deprivation therapy improved outcomes more than short-term therapy for prostate cancer. Another found radiation improved survival for node-positive prostate cancer.
3. For glioblastoma, a study identified molecular subgroups with more favorable prognosis, while another found improved outcomes with dose-escalated radiation and temozolomide.
4. For rectal cancer, studies explored organ-sparing approaches and found hypofraction
This document summarizes clinical trial data for several drugs tested in advanced hepatocellular carcinoma (HCC) after sorafenib failure. It shows that regorafenib, cabozantinib, and ramucirumab each provided a median overall survival benefit of 1-3 months compared to placebo. Regorafenib had a median OS of 10.6 months versus 7.8 months for placebo. Cabozantinib had a median OS of 10.2 months versus 8 months for placebo. Ramucirumab plus BSC had a median OS of 8.5 months versus 7.3 months for placebo plus BSC. Lenvatinib was found to be non-inferior
The document summarizes several studies presented at the 2008 Gastrointestinal Cancers Symposium. The PACCE trial found that adding panitumumab to oxaliplatin or irinotecan chemotherapy did not improve outcomes and increased toxicity. The FFCD trial found higher response rates with 5-FU/irinotecan vs 5-FU alone in elderly patients with colorectal cancer. The X-ACT trial showed a trend toward improved survival with capecitabine vs 5-FU/LV as adjuvant therapy. Studies also suggested intermittent oxaliplatin dosing may improve outcomes and that KRAS mutation status predicts response to anti-EGFR antibodies like panitumumab.
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.
This document summarizes recent developments in the treatment of immune thrombocytopenia (ITP). It discusses new evidence on treatments for refractory ITP including rituximab, thrombopoietin receptor agonists (TPO-RAs), and long-term use of eltrombopag. A randomized controlled trial found that rituximab did not significantly reduce long-term treatment failure compared to placebo in previously steroid-treated ITP patients. Long-term use of eltrombopag for up to 3 years was found to be generally safe and effective at maintaining platelet counts. The document concludes that large, randomized studies are still needed to better understand new ITP treatment options and balancing risks versus benefits requires consideration
This document summarizes key findings from the SPARTAN clinical trial evaluating the efficacy of apalutamide for the treatment of non-metastatic castration-resistant prostate cancer. The study found that apalutamide significantly reduced the risk of distant metastasis or death by 72% compared to placebo. Apalutamide also improved progression-free survival, time to symptomatic progression, and delayed the time to initiation of cytotoxic chemotherapy. The most common adverse events with apalutamide were fatigue, hypertension, and rash.
This case study examines the use of cetuximab-based chemotherapy for the re-treatment of patients with metastatic colorectal cancer who had previously responded to cetuximab treatment but experienced disease progression after stopping treatment. The study aims to evaluate the overall response and safety of re-treating these patients with cetuximab-containing chemotherapy. It describes the study design, inclusion/exclusion criteria, experimental and control treatments, and primary/secondary outcome measures that will be assessed over a 2-year period.
This document summarizes the use of PET-CT in staging and assessing treatment response in Hodgkin's lymphoma. It discusses that PET-CT is an important tool for initial staging, assessing response to chemotherapy, and prognostic indicator when done after partial chemotherapy. The sensitivity and specificity of PET-CT is higher than CT alone for detecting nodal and organ involvement. PET-CT may avoid the need for bone marrow biopsy in some cases. Interim PET imaging helps distinguish residual mass as viable tumor or necrosis/fibrosis. The document also reviews chemotherapy regimens like ABVD, BEACOPP and Stanford V in early and advanced Hodgkin's lymphoma.
This study compared short-course radiotherapy to long-course chemoradiation for patients with T3 rectal cancer. It found that long-course treatment resulted in a lower risk of local tumor recurrence, though the difference was not statistically significant. Both treatments had similar rates of distant tumor recurrence and overall survival. Long-course treatment seemed to provide a greater benefit for distal tumors, with fewer local recurrences, but again the difference was not statistically significant due to the small number of distal tumors.
Treatment Of Potentially Resectable Pancreatic Cancerfondas vakalis
1. Conventional treatment for resectable pancreatic cancer involving surgery and adjuvant chemoradiation has shown limited success, with few long-term survivors and significant treatment-related toxicity.
2. Preoperative chemoradiation using gemcitabine has shown promise in improving resectability and survival rates compared to postoperative chemoradiation or surgery alone, while avoiding unnecessary surgeries.
3. Combining gemcitabine with newer chemotherapy agents like capecitabine may allow higher drug doses with reduced toxicity when combined with radiation, improving patient outcomes.
This document summarizes a study comparing the efficacy of nivolumab versus docetaxel in treating advanced squamous-cell non-small cell lung cancer. The study found that nivolumab demonstrated superior overall survival and objective response rates compared to docetaxel, with less adverse events. Nivolumab treatment resulted in longer overall survival and progression-free survival. Expression of PD-L1 protein was found to be neither prognostic nor predictive of outcomes with nivolumab treatment. The results indicate that nivolumab is more effective and safer than docetaxel for second-line treatment of advanced squamous-cell lung cancer.
This study compared the efficacy and toxicities of gemcitabine/cisplatin combination chemotherapy and paclitexal/carboplatin combination chemotherapy as first-line treatment for 53 patients with stage IIIB or IV non-small cell lung cancer. The study found that gemcitabine/cisplatin combination resulted in better response rates but not statistically significantly so. It also found that gemcitabine/cisplatin combination resulted in more hematological toxicities. Patient demographics were not significantly different between the two treatment arms. The study concluded that platinum-based combinations are effective for non-small cell lung cancer but require proper premedications.
The document discusses adjuvant radiation therapy for gallbladder carcinoma based on available literature. It summarizes several retrospective studies that found improved survival outcomes with adjuvant radiation or chemoradiation after surgical resection compared to surgery alone, especially for node-positive or advanced-stage disease. However, it notes the evidence is limited due to the rarity of the disease and lack of large randomized controlled trials. While adjuvant therapy appears logical, more research is still needed to better define its role and optimal use.
1) Preoperative chemotherapy or chemoradiotherapy can downstage tumors and increase resection rates for stomach cancer compared to surgery alone.
2) The MAGIC trial showed perioperative chemotherapy improved survival rates over surgery alone by reducing tumor size and stage.
3) The TOPGEAR trial is currently testing adding preoperative chemoradiotherapy to perioperative chemotherapy to further improve outcomes. Interim results found it to be safe and feasible.
This document describes a study protocol for a randomized phase III clinical trial comparing neoadjuvant chemoradiation followed by surgery versus surgery alone in patients with adenocarcinoma or squamous cell carcinoma of the esophagus. The trial aims to enroll 350 patients total with 175 patients in each arm. The primary objective is to compare median survival rates and quality of life between the two treatment groups. Secondary objectives include comparing pathological responses, progression-free survival, number of complete resections, treatment toxicity, and costs. The chemoradiation regimen involves weekly paclitaxel and carboplatin chemotherapy with concurrent radiation over 5 weeks. Patients will then undergo surgery and be followed up for survival and quality of life outcomes
1) Radiotherapy is effective at preventing recurrence of non-functional pituitary adenomas, with 10-year local control rates of 87-91% when used post-operatively. Higher radiation doses are associated with improved long-term tumor control.
2) Younger patient age, prolactin- or ACTH-secreting tumors, and treatment for recurrent tumors are associated with worse treatment outcomes.
3) Permanent hypopituitarism is a complication of radiotherapy, with risks of hypothyroidism, hypoadrenalism, and hypogonadism shown to increase over time. Close monitoring of pituitary function is required.
1) Adjuvant chemotherapy is recommended for stage III colon cancer and high-risk stage II cancer to reduce the risk of recurrence. 2) For stage III, 5-FU plus folinic acid or capecitabine are standard options, while adding oxaliplatin to these regimens may provide additional benefit. 3) The value of adjuvant therapies like bevacizumab, cetuximab, and irinotecan is still unclear, with studies showing mixed results.
1) A study analyzed data from 687 patients with triple negative breast cancer who received surgery and adjuvant chemotherapy. The study found that as the time between surgery and starting chemotherapy increased, both 10-year disease-free survival and 10-year overall survival decreased.
2) Patients who started chemotherapy within 30 days of surgery had the best outcomes, with 10-year disease-free survival of 81.4% and 10-year overall survival of 82%.
3) Delaying the start of adjuvant chemotherapy by more than 90 days after surgery was associated with significantly worse survival outcomes.
This document discusses current concepts in chemotherapy for head and neck cancer. It begins by introducing head and neck squamous cell carcinoma (HNSCC) as the sixth most common cancer worldwide. It then reviews epidemiology and risk factors for HNSCC before defining different types of chemotherapy. The bulk of the document discusses evidence and standards of care for systemic therapy in previously untreated locally advanced HNSCC as well as recurrent/metastatic HNSCC. It covers the role of induction, concurrent, adjuvant and definitive chemotherapy combined with surgery or radiation. Overall survival benefits have been shown with platinum-based chemotherapy regimens and cetuximab combined with radiation or chemotherapy.
Definition: Small cell lung carcinoma (SCLC) is a type of lung cancer that typically starts in the bronchi (large airways) and tends to grow and spread quickly. It accounts for approximately 10-15% of all lung cancers.
Characteristics: SCLC is characterized by small, oat-shaped cancer cells that rapidly divide and form large tumors. It is often associated with a history of smoking and has a strong correlation with tobacco exposure.
Aggressive nature: SCLC is considered highly aggressive, with a tendency to metastasize (spread) early to the lymph nodes and other distant parts of the body, such as the liver, bones, and brain. This rapid spread makes early detection and treatment crucial.
Limited and extensive stage: SCLC is classified into two stages: limited stage and extensive stage. Limited stage means the cancer is confined to one side of the chest and potentially adjacent lymph nodes, whereas extensive stage indicates that the cancer has spread beyond the chest to distant organs.
Treatment approach: The treatment of SCLC typically involves a combination of chemotherapy and radiation therapy. Surgery is generally not recommended for SCLC due to its aggressive nature and tendency to spread early. Chemotherapy, often in combination with immunotherapy, is the mainstay of treatment and can help shrink tumors and control the disease.
Prognosis: The prognosis for SCLC is generally poorer compared to non-small cell lung carcinoma (NSCLC) due to its more aggressive behavior and earlier metastasis. However, treatment advances and research efforts continue to improve outcomes for SCLC patients.
Supportive care: As with any cancer diagnosis, supportive care plays a critical role in managing SCLC. This includes addressing symptoms, managing pain, providing emotional support, and ensuring optimal quality of life for patients.
It's important to consult with healthcare professionals for an accurate diagnosis, personalized treatment plan, and ongoing monitoring for individuals suspected or diagnosed with small cell lung carcinoma.
management of advanced cervical cancer [Autosaved].pptxSonyNanda2
The document summarizes current management strategies for locally advanced and metastatic cervical cancer. It discusses the following key points in 3 sentences:
Concurrent chemoradiation (CCRT) with cisplatin is considered the standard treatment for locally advanced cervical cancer (LACC). Studies have shown CCRT provides a 5-year survival advantage of 10-15% compared to radiation alone by reducing local recurrence and improving disease-free survival. Trials have investigated strategies like neoadjuvant chemotherapy (NACT) and extended field radiation but have yielded varying results with no clear consensus on improved outcomes compared to CCRT.
This document discusses treatment options for gastric cancer, including surgery, chemotherapy, and radiation therapy. It covers various lymph node dissection classifications (D0-D2) and their roles in different stages of disease. Adjuvant therapies like chemotherapy and chemoradiation are recommended after surgery to improve survival outcomes. Perioperative and postoperative chemotherapy are supported by clinical trials to be beneficial in resectable gastric cancer.
This document discusses treatment options for locally advanced breast cancer (LABC). It notes that LABC is a heterogeneous disease and standard primary chemotherapy includes anthracyclines and taxanes. Neoadjuvant chemotherapy is now the standard of care as it allows for breast conservation in some cases and those who achieve a pathological complete response have improved survival rates. The response to neoadjuvant therapy and molecular subtypes (e.g. triple negative, HER2-positive) can help determine the most effective adjuvant treatment strategy. Targeted therapies like trastuzumab improve outcomes for HER2-positive breast cancer when given with chemotherapy in the neoadjuvant setting.
Canadian Conference on Lymphoproliferative Disorders (CCOLD)Laurie Watkins
The document describes a call for abstracts for the Canadian Conference on Lymphoproliferative Disorders' Young Investigators Research Awards Program. Trainees at any level may submit an abstract of their work in lymphoproliferative or plasma cell disorders to be considered for presentation at the conference and to have their travel, hotel and registration costs covered. One sample abstract submitted for the program is summarized in less than 500 words on a study analyzing outcomes for mantle cell lymphoma patients treated with R-CHOP chemotherapy followed by autologous stem cell transplantation and rituximab maintenance therapy.
Similar to 10 Antiangiogenicos en Cáncer de Pulmón (20)
Con la intención de mejorar la comunicación sobre el cáncer se creó en 2002 la plataforma para divulgación del cáncer, Access Oncología, programa en el que participan un grupo de prestigiosos oncólogos de todo el país. Como resultado de una de sus actividades nace este Glosario del cáncer. Sus cerca de 700 términos específicos sobre la enfermedad quieren salvar la distancia comunicativa entre oncólogo y paciente. Este listado será muy útil para todos aquellos que de manera regular o esporádica deban entender y comunicar esta enfermedad: pacientes, familiares, periodistas, responsables de comunicación de hospitales, consejerías de salud, asociaciones de pacientes, etc.
El documento proporciona información sobre estudios de usabilidad web. Explica que la usabilidad web se define por 5 componentes de calidad como aprendizaje, eficiencia, recuerdo, errores y satisfacción. Describe diferentes tipos de pruebas de usabilidad como pruebas subjetivas y objetivas como el seguimiento ocular y el rastreo de clics. Resalta que los mapas de calor son útiles para mostrar las áreas más visitadas por los usuarios.
- The document discusses treatment options for locally advanced non-small cell lung cancer (NSCLC), including chemoradiation therapy.
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Este documento resume varias terapias quirúrgicas para el tratamiento del cáncer de pulmón, incluidas las lobectomías toracoscópicas, los tipos de resección pulmonar, el tratamiento de los nódulos en vidrio deslustrado y las metástasis. Describe los beneficios y aplicabilidad de diferentes técnicas quirúrgicas, así como factores pronósticos para el cáncer de pulmón en estadios avanzados.
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This document discusses biomarkers for lung cancer diagnosis, prognosis, and prediction of treatment response. It emphasizes the importance of tumor tissue samples for biomarker analysis but also explores opportunities for using liquid biopsies of blood and other body fluids. A variety of biomarker types are considered, including mutations, gene fusions, protein expression, and microRNAs. The need for standardized biomarker testing methodologies and validation is stressed, along with organizing reference laboratories through country networks.
Este documento presenta resúmenes de varias sesiones orales y posters de la 15a Conferencia Mundial de la IASLC sobre cáncer de pulmón que tuvo lugar en Sídney. Incluye resúmenes sobre estudios de screening de cáncer de pulmón con TAC de baja dosis, factores de riesgo como el tabaquismo y la exposición a metales pesados, y estrategias de prevención y cesación tabáquica. El documento proporciona una visión general de las últimas investigaciones presentadas en la conferencia sobre
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
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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.
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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
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
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...Donc Test
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• Pitfalls and pivots needed to use AI effectively in public health
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• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
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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.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
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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.
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10 Antiangiogenicos en Cáncer de Pulmón
1. Tratamientos sistémicos en el NSCLC
ANTIANGIOGÉNICOS
Dr J Pérez Altozano
HGU Elche / H Vega Baja Orihuela
8 de noviembre de 2013
2. History of Therapy in Advanced
NSCLC: FDA Approval Dates
Gefitinib
2003
Docetaxel
2002
Standard therapies
First line
Second line
Third line
Maintenance
Not approved
Cisplatin
1978
Carboplatin
1989
BSC
Paclitaxel
Gemcitabine
1998
Bevacizumab
2006
Pemetrexed
2008/2009
Vinorelbine
1994
12+
Median
OS (mos)
~ 8-10
~6
~ 2-4
1970
Erlotinib
Pemetrexed
2004
Docetaxel
1999
1980
Single-agent platinum
1990
2000
Bevacizumab + PC
Doublets
Histology-directed therapy
1. FDA Web site. 2. NCCN. Clinical practice guidelines in oncology. v.3.2011. 3. Schrump, et al. Non-small
cell lung cancer. In: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2005.
3. Incidence of NSCLC
Histologic Subtypes
20%
40%
15%
30%
Adenocarcinoma
Squamous-cell carcinoma
Large-cell carcinoma
NOS
4. Lung Cancer Molecular Consortium
Analysis in Lung Adenocarcinomas
No Mutation
Detected
AKT1
NRAS
MEK1
MET AMP
HER2
PIK3CA 2%
BRAF 2%
Double
Mutants 3%
EML4-AKL
7%
KRAS
22%
EGFR
17%
Kris MG, et al. ASCO 2011. CRA7506. Johnson BE, et al. IASLC WCLC 2011. Abstract O16.01
27. Background
Evaluate the feasibility of induction combination therapy with cisplatin, pemetrexed and bevacizumab followed by surgery in patients
with clinical stage II/IIIA nonsquamous NSCLC.
Methods
Induction chemotherapy : 3 cycles of cisplatin (75 mg/m2), pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) on Day 1,
every 21 days.
Patients underwent surgical resection at least 6 weeks after the last administration of bevacizumab,
Primary endpoint: complete resection rate after the completion of three cycles of induction chemotherapy.
Feasibility: complete resection rate 80% (24/30) or more.
Results
6 institutions in Japan, June 2010 - November 2012.
31 patients were recruited, 30 of which were eligible.
Median age was 64 years (range: 54-71).
Adenocarcinoma/large cell carcinoma ratio: 30/0
Clinical stage IIA/IIB/IIIA ratio: 5/3/22.
Grade 3 toxicities: Neutropenia (7%), nausea (7%), appetite loss (13%), hypertension (23%) and pulmonary embolism (3%).
27 (90%) patients completed three cycles at the full dose of chemotherapy.
CR in 0%, PR in 37%, SD in 50% and PD in 10%. Disease control rate (CR+PR+SD) 87%.
Five patients dropped out from the study before surgery.
Complete resection rate after the completion of three cycles of induction chemotherapy: 83% (25/80).
Conclusion
Induction chemotherapy using a combination of cisplatin, pemetrexed and bevacizumab in patients with resectable clinical stage II/IIIA
nonsquamous NSCLC is therefore considered to be a feasible treatment modality.
28. Background
Evaluate the feasibility of induction combination therapy with cisplatin, pemetrexed and bevacizumab followed by surgery in patients
with clinical stage II/IIIA nonsquamous NSCLC.
Methods
Induction chemotherapy : 3 cycles of cisplatin (75 mg/m2), pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) on Day 1,
every 21 days.
Patients underwent surgical resection at least 6 weeks after the last administration of bevacizumab,
Primary endpoint: complete resection rate after the completion of three cycles of induction chemotherapy.
Feasibility: complete resection rate 80% (24/30) or more.
Results
6 institutions in Japan, June 2010 - November 2012.
31 patients were recruited, 30 of which were eligible.
Median age was 64 years (range: 54-71).
Adenocarcinoma/large cell carcinoma ratio: 30/0
Clinical stage IIA/IIB/IIIA ratio: 5/3/22.
Grade 3 toxicities: Neutropenia (7%), nausea (7%), appetite loss (13%), hypertension (23%) and pulmonary embolism (3%).
27 (90%) patients completed three cycles at the full dose of chemotherapy.
CR in 0%, PR in 37%, SD in 50% and PD in 10%. Disease control rate (CR+PR+SD) 87%.
Five patients dropped out from the study before surgery.
Complete resection rate after the completion of three cycles of induction chemotherapy: 83% (25/80).
Conclusion
Induction chemotherapy using a combination of cisplatin, pemetrexed and bevacizumab in patients with resectable clinical stage II/IIIA
nonsquamous NSCLC is therefore considered to be a feasible treatment modality.
29. Background
Explore the role of bevacizumab in the neoadjuvant setting.
Assess the safety and efficacy of neoadjuvant bevacizumab plus pemetrexed and carboplatin followed by surgery in
conventionally unresectable, locally advanced (III A-bulky N2, III B) lung adenocarcinoma.
Methods
Single-center, single-arm, phase II study investigates neoadjuvant bevacizumab (7.5mg/kg) plus pemetrexed (500 mg/m2) and
carboplatin (AUC=5) x 4 cycles followed by surgery scheduled 3-4 weeks after last neoadjuvant therapy.
Primary and secondary endpoints were resectability rate and perioperative complications.
Results
20 patients were enrolled.
Neoadjuvant-related toxicities: Epistaxis (5%), fatigue (30%), infusion reaction (5%), nausea (5%), diarrhea (10%), insomnia
(5%), headache (5%); neutropenia (25%), anemia (10%), thrombocytopenia (5%).
Grade > 3 toxicities: Fatigue (10%); neutropenia (5%), thrombocytopenia (5%).
CR in 1 patient, PR in 8, SD in 10 and PD in 1.
14 (70%) patients underwent surgery.
Median time between last neoadjuvant therapy and surgery: 25 days (22-28).
R0 resection achieved in 10 patients.
Postoperative complications were manageable.
Conclusion
The treatment modality of neoadjuvant bevacizumab plus pemetrexed and carboplatin followed by surgery appears to be safe
and feasible in patients with unresectable, locally advanced (III A-bulky N2, III B) lung adenocarcinoma.
30. Background
Explore the role of bevacizumab in the neoadjuvant setting.
Assess the safety and efficacy of neoadjuvant bevacizumab plus pemetrexed and carboplatin followed by surgery in
conventionally unresectable, locally advanced (III A-bulky N2, III B) lung adenocarcinoma.
Methods
Single-center, single-arm, phase II study investigates neoadjuvant bevacizumab (7.5mg/kg) plus pemetrexed (500 mg/m2) and
carboplatin (AUC=5) x 4 cycles followed by surgery scheduled 3-4 weeks after last neoadjuvant therapy.
Primary and secondary endpoints were resectability rate and perioperative complications.
Results
20 patients were enrolled.
Neoadjuvant-related toxicities: Epistaxis (5%), fatigue (30%), infusion reaction (5%), nausea (5%), diarrhea (10%), insomnia
(5%), headache (5%); neutropenia (25%), anemia (10%), thrombocytopenia (5%).
Grade > 3 toxicities: Fatigue (10%); neutropenia (5%), thrombocytopenia (5%).
CR in 1 patient, PR in 8, SD in 10 and PD in 1.
14 (70%) patients underwent surgery.
Median time between last neoadjuvant therapy and surgery: 25 days (22-28).
R0 resection achieved in 10 patients.
Postoperative complications were manageable.
Conclusion
The treatment modality of neoadjuvant bevacizumab plus pemetrexed and carboplatin followed by surgery appears to be safe
and feasible in patients with unresectable, locally advanced (III A-bulky N2, III B) lung adenocarcinoma.
31. Background
Two combination chemotherapy regimens were compared in a Phase 3, randomized, open-label United States only study
Methods
Stage IV chemonaïve non-squamous NSCLC.
PemC (n=182) or PCB (n=179).
Safety data compared for patients who received ≥1 dose of study treatment (PemC:171; PCB:166), and resource use including
concomitant medications, transfusions, and hospitalizations was recorded.
Results
PemC experienced significantly more drug-related Grade 3/4 anemia (18.7% vs. 5.4%; p<0.001), Grade 3/4 thrombocytopenia (24.0% vs.
9.6%; p<0.001), and Grade 1/2 nausea (46.8% vs. 28.9%; p<0.001)
PCB experienced significantly more drug-related Grade 3/4 neutropenia (24.6% vs. 48.8%; p<0.001) and Grade 1/2 alopecia (8.2% vs.
28.3%; p<0.001).
Patients on PemC required more red blood cell (RBC) transfusions (34.5% vs. 11.4%; p<0.001).
Erythropoietic stimulating agents (ESAs) were used more frequently (19.9% vs. 7.2%; p<0.001) in PemC.
Granulocyte colony-stimulating factor (G-CSF) use was significantly higher with PCB (17.0% vs. 30.1%; p=0.005).
Conclusion
Mild-to-moderate nausea more common for PemC and alopecia, infection and neuropathy more frequent for PCB.
Hospitalizations did not differ between treatments.
ESAs and RBC transfusions were more common with PemC, and G-CSF use was more common with PCB.
32. Background
Two combination chemotherapy regimens were compared in a Phase 3, randomized, open-label United States only study
Methods
Stage IV chemonaïve non-squamous NSCLC.
PemC (n=182) or PCB (n=179).
Safety data compared for patients who received ≥1 dose of study treatment (PemC:171; PCB:166), and resource use including
concomitant medications, transfusions, and hospitalizations was recorded.
Results
PemC experienced significantly more drug-related Grade 3/4 anemia (18.7% vs. 5.4%; p<0.001), Grade 3/4 thrombocytopenia (24.0% vs.
9.6%; p<0.001), and Grade 1/2 nausea (46.8% vs. 28.9%; p<0.001)
PCB experienced significantly more drug-related Grade 3/4 neutropenia (24.6% vs. 48.8%; p<0.001) and Grade 1/2 alopecia (8.2% vs.
28.3%; p<0.001).
Patients on PemC required more red blood cell (RBC) transfusions (34.5% vs. 11.4%; p<0.001).
Erythropoietic stimulating agents (ESAs) were used more frequently (19.9% vs. 7.2%; p<0.001) in PemC.
Granulocyte colony-stimulating factor (G-CSF) use was significantly higher with PCB (17.0% vs. 30.1%; p=0.005).
Conclusion
Mild-to-moderate nausea more common for PemC and alopecia, infection and neuropathy more frequent for PCB.
Hospitalizations did not differ between treatments.
ESAs and RBC transfusions were more common with PemC, and G-CSF use was more common with PCB.
33. Background
Two combination chemotherapy regimens were compared in a Phase 3, randomized, open-label United States only study
Methods
Stage IV chemonaïve non-squamous NSCLC.
PemC (n=182) or PCB (n=179).
Safety data compared for patients who received ≥1 dose of study treatment (PemC:171; PCB:166), and resource use including
concomitant medications, transfusions, and hospitalizations was recorded.
Results
PemC experienced significantly more drug-related Grade 3/4 anemia (18.7% vs. 5.4%; p<0.001), Grade 3/4 thrombocytopenia (24.0% vs.
9.6%; p<0.001), and Grade 1/2 nausea (46.8% vs. 28.9%; p<0.001)
PCB experienced significantly more drug-related Grade 3/4 neutropenia (24.6% vs. 48.8%; p<0.001) and Grade 1/2 alopecia (8.2% vs.
28.3%; p<0.001).
Patients on PemC required more red blood cell (RBC) transfusions (34.5% vs. 11.4%; p<0.001).
Erythropoietic stimulating agents (ESAs) were used more frequently (19.9% vs. 7.2%; p<0.001) in PemC.
Granulocyte colony-stimulating factor (G-CSF) use was significantly higher with PCB (17.0% vs. 30.1%; p=0.005).
Conclusion
Mild-to-moderate nausea more common for PemC and alopecia, infection and neuropathy more frequent for PCB.
Hospitalizations did not differ between treatments.
ESAs and RBC transfusions were more common with PemC, and G-CSF use was more common with PCB.
34. Background
Designed on preclinical results suggesting additive interaction of metronomic chemotherapy with VEGF deprivation and EGFR
inhibition, in term of anti-tumor/anti-angiogenic-activity and immune-modulation.
Methods
35 inoperable NSCLC patients. 26 adenocarcinoma, 6 squamocellular and 3 NAS carcinoma.
Median age of 68 years (range 3-75).
Cisplatin (30mg/sqm days 1-3q21 + Etoposide 50mg/sqm days 1-15/21 + Bevacizumab 5mg/kg on the day 3q21.
After 4 treatment courses, all patients who achieved a PR or SD received daily Erlotinib (150 mg/day), starting 1 week after end of
chemotherapy until PD.
Cytokine multiplex analysis and an immune-cytofluorimetric analysis after 4 bio-chemotherapy courses and 3 months after end of biochemotherapy.
Results
Significant decrease in serum levels of VEGF and IL-10 which was maintained along TKI treatment.
No change in angiopoietin, interferon gamma, IL-12, PECAM and follistatin levels.
During TKI maintenance we recorded an increase in IL-8 and leptine associated with a significant decrease in G-CSF levels and
angiopoietin levels.
Our immune-cytofluorimetric analysis of patients’ PBMCs showed a significant treatment-related increase in activated (CD3CD11C+CD14+CD80+CD83+) dendritic cells and activated (CD3+CD8+CD62L+) cytotoxic-T –lymphocytes.
Conclusion
Treatment strategy is safe and active in NSCLC patients, and is able to affects their systemic inflammatory status also inducing immunemodulation with potential antitumor.
35. Background
Designed on preclinical results suggesting additive interaction of metronomic chemotherapy with VEGF deprivation and EGFR
inhibition, in term of anti-tumor/anti-angiogenic-activity and immune-modulation.
Methods
35 inoperable NSCLC patients. 26 adenocarcinoma, 6 squamocellular and 3 NAS carcinoma.
Median age of 68 years (range 3-75).
Cisplatin (30mg/sqm days 1-3q21 + Etoposide 50mg/sqm days 1-15/21 + Bevacizumab 5mg/kg on the day 3q21.
After 4 treatment courses, all patients who achieved a PR or SD received daily Erlotinib (150 mg/day), starting 1 week after end of
chemotherapy until PD.
Cytokine multiplex analysis and an immune-cytofluorimetric analysis after 4 bio-chemotherapy courses and 3 months after end of biochemotherapy.
Results
Significant decrease in serum levels of VEGF and IL-10 which was maintained along TKI treatment.
No change in angiopoietin, interferon gamma, IL-12, PECAM and follistatin levels.
During TKI maintenance we recorded an increase in IL-8 and leptine associated with a significant decrease in G-CSF levels and
angiopoietin levels.
Our immune-cytofluorimetric analysis of patients’ PBMCs showed a significant treatment-related increase in activated (CD3CD11C+CD14+CD80+CD83+) dendritic cells and activated (CD3+CD8+CD62L+) cytotoxic-T –lymphocytes.
Conclusion
Treatment strategy is safe and active in NSCLC patients, and is able to affects their systemic inflammatory status also inducing immunemodulation with potential antitumor.
36. Background
Frequent administration of low dose chemotherapy agents (metronomic chemotherapy [MC]) is thought to target endothelial
cells of the tumor vasculature as well as tumor cells.
Pilot phase 2 study: Bevacizumab and MC will result in enhanced antiangiogenic effect and clinical benefit in advanced NSCLC.
Methods
Untreated patients with stage 4 non-squamous NSCLC.
4-week cycle of paclitaxel (80 mg/m2 D1, 8, 15), gemcitabine (200-300 mg/m2 D1, 8, 15) and bevacizumab (10 mg/kg D1, 15)
for 6 cycles. Patients without progressive disease received maintenance bevacizumab every 2 weeks.
Primary endpoint: PFS with the goal to achieve a 30% improvement in the 6.4 months.
Secondary endpoints: ORR, OS, safety and evaluation of potential biomarkers of angiogenesis.
Results
33 evaluable patients were enrolled
Median age 59 years.
Grade 3 neutropenia (15%); grade 3 fatigue (6%); grade 3 nausea (3%); grade 3/4 hypertension (30%); grade 3/4 proteinuria
(18%); pneumonitis (3 patients); and ischemic events (2 patients).
Baseline biomarkers with significant correlation with response parameters: VEGF2 (ORR); PLGF (OS); angiopoietin -2 (PFS, OS);
endocan (ORR); IL-8 (ORR, PFS); TGFβ-1 (ORR); thrombospondin-1 (ORR); and angiopoietin-1 (ORR).
PFS: 9m (95% CI:7; 10), OS 30m (95% CI: 18; 37), 1-year survival rate 74%, 2-year survival rate 55%, ORR 73% (95% CI:0.54;
0.87)
Conclusion
MC with a platinum doublet in combination with bevacizumab is a feasible, tolerable, and active regimen in advanced nonsquamous NSCLC. Potential biomarkers were correlated with clinical outcome.
37. Background
Prospective phaseⅡ study to evaluate the efficacy and safety of bevacizumab in combination with carboplatin and
paclitaxel(PCB) for EGFR-TKIs resistant Non-Sq NSCLC.
Methods
Multicenter phase II trial.
Non-squamous NSCLC harboring EGFR gene mutation after failing EGFR-TKIs.
Patients received carboplatin (AUC=6/5), paclitaxel (200mg/m2), bevacizumab (15mg/kg) intravenously on day1 every 3
weeks for three to six cycles, and bevacizumab every 3 weeks until disease progression or intolerable toxic effects.
Primary endpoint: RR
Secondary endpoints: PFS, OS, disease control rate and safety.
Results
30 patients between March 2010 - February 2013.
Median age: 60 years (45~74).
EGFR mutation status exon19 del/exon21 L858R : 20/11.
1st line EGFR-TKIs gefitinib/erlotinib/other : 22/7/1.
RR : 40% (95%CI:22%-58%).
DCR : 83% (95%CI:70%-97%), PFS : 6.0 month (95%CI:4.8-12.2).
Conclusion
RR of 2nd line PCB therapy was lower than it was in 1st line phase II study of PCB in Japan, but same RR of E4599 study.
We considered PCB therapy is one of the treatment option in 2nd-line for patient with EGFR-TKIs resistant Non-Sq NSCLC.
38. Background
Prospective phaseⅡ study to evaluate the efficacy and safety of bevacizumab in combination with carboplatin and
paclitaxel(PCB) for EGFR-TKIs resistant Non-Sq NSCLC.
Methods
Multicenter phase II trial.
Non-squamous NSCLC harboring EGFR gene mutation after failing EGFR-TKIs.
Patients received carboplatin (AUC=6/5), paclitaxel (200mg/m2), bevacizumab (15mg/kg) intravenously on day1 every 3
weeks for three to six cycles, and bevacizumab every 3 weeks until disease progression or intolerable toxic effects.
Primary endpoint: RR
Secondary endpoints: PFS, OS, disease control rate and safety.
Results
30 patients between March 2010 - February 2013.
Median age: 60 years (45~74).
EGFR mutation status exon19 del/exon21 L858R : 20/11.
1st line EGFR-TKIs gefitinib/erlotinib/other : 22/7/1.
RR : 40% (95%CI:22%-58%).
DCR : 83% (95%CI:70%-97%), PFS : 6.0 month (95%CI:4.8-12.2).
Conclusion
RR of 2nd line PCB therapy was lower than it was in 1st line phase II study of PCB in Japan, but same RR of E4599 study.
We considered PCB therapy is one of the treatment option in 2nd-line for patient with EGFR-TKIs resistant Non-Sq NSCLC.
39. Background
Interim-analysis result of the BEST trial.
Examines efficacy and safety of second- or third-line chemotherapy with erlotinib (E) and bevacizumab (B) for the Japanese patients
(pts) with non-squamous, non-small cell lung cancer.
Methods
E 150 mg/day orally + B 15 mg/kg on the first day of each 3-week cycle.
Primary endpoint: RR.
Secondary endpoints: OS, PFS, disease control rate and incidence of adverse events.
Planned to accrue 80 pts based on a two-stage design employing a binomial distribution with an alternative hypothesis response rate
of 35% and a null hypothesis threshold response rate of 20%.
Results
28 pts enrolled in 2 years.
Median age: 67y (43-82).
All had adenocarcinoma; 11 pts had EGFR mutation.
1 patient had stage IIIB, 23 pts had stage IV and 3 pts had recurrences after surgery.
21 pts received as second-line and 6 pts received as third-line chemotherapy.
RR 18.5% (p=1.00; one-sided).
DCR 77.8%, PFS 5.6 m; OS data not yet mature (median follow-up time was 11.9 m).
Grade 3/4 non-hematologic toxicities: Acne (11.1%) and hypertension (11.1%).
Significantly higher RR (p=0.02) and better PFS (p=0.03) in mutant group than in wild group. RR in mutant group was compared with
20% null hypothesis using the same binomial test (p=0.056).
Conclusion
Combination therapy of B + E had mild adverse effects but did not increase anti-cancer effect.
40. Background
Interim-analysis result of the BEST trial.
Examines efficacy and safety of second- or third-line chemotherapy with erlotinib (E) and bevacizumab (B) for the Japanese patients
(pts) with non-squamous, non-small cell lung cancer.
Methods
E 150 mg/day orally + B 15 mg/kg on the first day of each 3-week cycle.
Primary endpoint: RR.
Secondary endpoints: OS, PFS, disease control rate and incidence of adverse events.
Planned to accrue 80 pts based on a two-stage design employing a binomial distribution with an alternative hypothesis response rate
of 35% and a null hypothesis threshold response rate of 20%.
Results
28 pts enrolled in 2 years.
Median age: 67y (43-82).
All had adenocarcinoma; 11 pts had EGFR mutation.
1 patient had stage IIIB, 23 pts had stage IV and 3 pts had recurrences after surgery.
21 pts received as second-line and 6 pts received as third-line chemotherapy.
RR 18.5% (p=1.00; one-sided).
DCR 77.8%, PFS 5.6 m; OS data not yet mature (median follow-up time was 11.9 m).
Grade 3/4 non-hematologic toxicities: Acne (11.1%) and hypertension (11.1%).
Significantly higher RR (p=0.02) and better PFS (p=0.03) in mutant group than in wild group. RR in mutant group was compared with
20% null hypothesis using the same binomial test (p=0.056).
Conclusion
Combination therapy of B + E had mild adverse effects but did not increase anti-cancer effect.
41. Background
Irinotecan and bevacizumab are effective against non-small cell lung cancer (NSCLC) and synergism with non-cross-resistance has
been demonstrated in preclinical studies.
Methods
24 patients having heavily treated metastatic NSCLC between March 2011 -November 2012.
16 patients had never been exposed to bevacizumab and 8 had received antiangiogenic therapy as part of their first-line (all had
achieved a previous response for more than 6 months).
90-min intravenous infusion of 125 mg/m2 irinotecan on day 1 and 8 + 7.5 mg/kg bevacizumab on day 1 every 3 weeks.
Results
1 patient (4.2%) CR, 6 (25%) PR.
ORR 29.2% (4.6 months median response duration).
7 patients SD and DCR was 58.3%.
PFS 4.8 months (95%CI 1.8-9.2) and OS 19.8 months (95%CI 9.2-30.2).
Grade 3-4 neutropenia in 43% of patients and thrombocytopenia in 8.3%.
4 patients harbouring EGFR mutations had a long-lasting, partial response (>7 months after at least 4 prior lines).
Conclusion
Favourable activity and manageable toxicity profiles as third or fourth line.
Regimen can represent a reasonable chemotherapeutic option, especially for subjects having EGFR mutations.
42. Background
Irinotecan and bevacizumab are effective against non-small cell lung cancer (NSCLC) and synergism with non-cross-resistance has
been demonstrated in preclinical studies.
Methods
24 patients having heavily treated metastatic NSCLC between March 2011 -November 2012.
16 patients had never been exposed to bevacizumab and 8 had received antiangiogenic therapy as part of their first-line (all had
achieved a previous response for more than 6 months).
90-min intravenous infusion of 125 mg/m2 irinotecan on day 1 and 8 + 7.5 mg/kg bevacizumab on day 1 every 3 weeks.
Results
1 patient (4.2%) CR, 6 (25%) PR.
ORR 29.2% (4.6 months median response duration).
7 patients SD and DCR was 58.3%.
PFS 4.8 months (95%CI 1.8-9.2) and OS 19.8 months (95%CI 9.2-30.2).
Grade 3-4 neutropenia in 43% of patients and thrombocytopenia in 8.3%.
4 patients harbouring EGFR mutations had a long-lasting, partial response (>7 months after at least 4 prior lines).
Conclusion
Favourable activity and manageable toxicity profiles as third or fourth line.
Regimen can represent a reasonable chemotherapeutic option, especially for subjects having EGFR mutations.
43. Background
Feasibility of BEV in NonSq-NSCLC patients who were previously treated with a platinum regimen.
Methods
Recurrent NonSq-NSCLC.
VNR (25mg/kg on day 1, 8) + BEV (15mg/kg, day 1) every 3 weeks until PD.
Primary endpoint: Feasibility.
Secondary endpoints: Response rate and safety.
Results
June 2011 - January 2013
15 NSCLC patients.
Median age: 68y (range 57-82).
Median of 4 (range 1-12) cycles.
Grade 3-4 neutropenia, anemia, thrombocytopenia and febrile neutropenia: 26.7%, 6.7%, 6.7%, and 13.3%.
RR 26.7% and disease control rate 73.3%.
PFS 2.8 months.
Grade 3-4 phlebitis occurred in 3 patients.
Conclusion
VNR + BEV was safe and effective in NonSq-NSCLC patients who were previously treated with a platinum
regimen.
44. Background
Feasibility of BEV in NonSq-NSCLC patients who were previously treated with a platinum regimen.
Methods
Recurrent NonSq-NSCLC.
VNR (25mg/kg on day 1, 8) + BEV (15mg/kg, day 1) every 3 weeks until PD.
Primary endpoint: Feasibility.
Secondary endpoints: Response rate and safety.
Results
June 2011 - January 2013
15 NSCLC patients.
Median age: 68y (range 57-82).
Median of 4 (range 1-12) cycles.
Grade 3-4 neutropenia, anemia, thrombocytopenia and febrile neutropenia: 26.7%, 6.7%, 6.7%, and 13.3%.
RR 26.7% and disease control rate 73.3%.
PFS 2.8 months.
Grade 3-4 phlebitis occurred in 3 patients.
Conclusion
VNR + BEV was safe and effective in NonSq-NSCLC patients who were previously treated with a platinum
regimen.
45. Background
Feasibility study of PEM plus BV as the first-line treatment for elderly advanced or recurrent non-Sq NSCLC.
Methods
Chemotherapy-naïve; unfit for bolus combination chemotherapy; stage III/IV or relapsed non-Sq NSCL.
Age≥70; PS 0-1; no evidence of brain metastasis; no history of hemoptysis and irradiation for thorax.
PEM (500mg/m2) + BV (15mg/kg) on day 1 every 3 weeks.
Primary endpoint: Toxicity
Secondary endpoints: ORR, PFS, OS and percentage of patients who completed more than 3 cycles.
Results
November 2010 -April 2012
12 patients.
Median age: 78 y (72-81).
Activating EGFR mutation No/Yes/unknown=9/2/1.
Stage IIIB/IV/Recurrence=2/8/2.
Grade 3≥ leukopenia (25%), neutropenia (25%), anemia (8%), thrombocytopenia (8%), febrile neutropenia (8%), anorexia (8%),
hypertension (8%), fatigue (8%), nausea (8%), and perforation (colon) (8%).
ORR 25%, PFS 5.6 (95% C.I. 1.1-7.9) and OS 10.3 months (95% C.I. 6.9-15.6 mo) in 11 evaluated patients.
1-year survival rate 49% (95% C.I. 12-79%).
7/12 pts (58%) received more than 3 cycles.
Conclusion
PEM +BV as first-line treatment for elderly non-Sq NSCLC was well tolerable and promising.
46. Background
Feasibility study of PEM plus BV as the first-line treatment for elderly advanced or recurrent non-Sq NSCLC.
Methods
Chemotherapy-naïve; unfit for bolus combination chemotherapy; stage III/IV or relapsed non-Sq NSCL.
Age≥70; PS 0-1; no evidence of brain metastasis; no history of hemoptysis and irradiation for thorax.
PEM (500mg/m2) + BV (15mg/kg) on day 1 every 3 weeks.
Primary endpoint: Toxicity
Secondary endpoints: ORR, PFS, OS and percentage of patients who completed more than 3 cycles.
Results
November 2010 -April 2012
12 patients.
Median age: 78 y (72-81).
Activating EGFR mutation No/Yes/unknown=9/2/1.
Stage IIIB/IV/Recurrence=2/8/2.
Grade 3≥ leukopenia (25%), neutropenia (25%), anemia (8%), thrombocytopenia (8%), febrile neutropenia (8%), anorexia (8%),
hypertension (8%), fatigue (8%), nausea (8%), and perforation (colon) (8%).
ORR 25%, PFS 5.6 (95% C.I. 1.1-7.9) and OS 10.3 months (95% C.I. 6.9-15.6 mo) in 11 evaluated patients.
1-year survival rate 49% (95% C.I. 12-79%).
7/12 pts (58%) received more than 3 cycles.
Conclusion
PEM +BV as first-line treatment for elderly non-Sq NSCLC was well tolerable and promising.
47.
48. Background
A series of Japanese trials indicate docetaxel (DTX) monotherapy is a standard of care in elderly patients with advanced nonsmall cell lung cancer (NSCLC), and that the addition of platinum does not significantly improve the outcomes. BEV toxicity is a
major concern for elderly patients.
Methods
Chemotherapy-naïve patients with advanced non-squamous NSCLC >70 year old
ECOG PS 0/1 an
DTX 60 (Level 0) or 50 (Level -1) mg/m2 and BEV 15 mg/kg on day 1, every 3 weeks.
Primary endpoint: Toxicity
Secondary endpoints: ORR, PFS, OS and completion rate of the 3 cycles of treatment.
Results
December 2010 - September 2012.
21 elderly patients (9 in level 0 and 12 in level -1).
Median age: 75 years, 67% PS 1.
Grade 3 or 4 of toxicities among all patients: Neutropenia (86%), anemia (5%), hypertension (19%), anorexia (10%), and
increased aminotransferase levels (10%).
3/9 patients in level 0 and 3/11 patients in level -1 obtained PR.
Completion rates of the 3 cycles of treatment :78% (7/9) in level 0 and 67 % (8/12) in level -1.
Median PFS and OS: 5.4 and 11.1 months.
Conclusion
The recommended dose for this combination in future study is docetaxel 50 mg/m2 and bevacizumab 15mg/kg.
49. Phase II trial: C (50 mg/m2), D (50 mg/m2), and B (10 mg/kg) every 2 weeks for up to 6 cycles, followed by B alone every
2 weeks until disease progression or unacceptable toxicity.
Primary efficacy endpoint: PFS Secondary endpoints: Safety profile, ORR, disease control rate and OS
32 patients enrolled.
Median age: 60 years (range 44-72; 28.1% > 65 years).
Adenocarcinoma (%): 84.
Median PFS: 6.4 months (95% CI, 4.2-8.7).
Among the 22 patients evaluable for response: ORR 63.6% and DCR 95.4%.
Combination: Bevacizumab (15 mg/kg), docetaxel (60 mg/m2) and carboplatin (AUC=6) on day 1 was administered every 3
weeks up to 6 cycles (induction phase). Bevacizumab maintenance therapy was performed until PD (maintenance phase).
Primary endpoint: PFS to prove superiority to previous standard chemotherapy (docetaxel and cisplatin).
40 patients enrolled and 39 patients analyzed.
Stage IV in 92%, EGFR mutations in 13% and unknown EGFR status in 8%.
Median age: 62 years.
Induction phase: 4 cycles in median (range: 1-6).
21 patients (54%) received maintenance phase with median 4 cycles (range: 2-24).
ORR of 74% (26/35) and median PFS of 6.4 months (95% CI: 4.8-9.9).
58. Background
Evaluate the benefits and harms of AATKIs when added to chemotherapy for advanced NSCLC.
Methods
Systematic review of randomised controlled trials (RCTs) of AATKIs added to chemotherapy for advanced or metastatic NSCLC.
Electronic databases (MEDLINE/PubMed, EMBASE, The Cochrane Library) + conference proceedings from ASCO, ESMO, IASLC WCLC and
Clinical Trials Registries.
Primary endpoint: OS.
Secondary endpoints: PFS, ORR and (G≥3 CTCAE. Meta-analysis of the data was performed to obtain pooled hazard ratios (HR) for OS and
PFS, and pooled odds ratios (OR) for ORR and G≥3CTCAE.
Review Manager v5.2 software (Cochrane).
Results
15 RCTs involving 7904 patients with advanced NSCLC. Overall population (N = 7904)
Addition of AATKI to chemotherapy:
Prolonged OS (HR 0.93; 95% confidence interval [CI] 0.88, 0.99; P=0.02) and PFS (HR 0.83; 95% CI 0.79, 0.88; P<0.00001).
Increased ORR (OR 1.64, 95% CI 1.34, 2.02; P<0.00001) and G≥3CTCAEs (OR 1.78, 95% CI 1.41, 2.25; P<0.00001).
First line (N = 3867), prolonged PFS (HR 0.86; 95% CI 0.79, 0.93; P<0.0001) but not OS (HR 0.96; 95% CI 0.89, 1.05; P=0.38).
Second line (N=4037), prolonged both OS (HR 0.91; 95% CI 0.84, 0.98; P=0.02) and PFS (HR 0.80; 95% CI 0.74, 0.87; P<0.00001).
Greatest OS benefit in patients with adenocarcinoma (HR 0.85; 95% CI 0.75, 0.96, P=0.01) and receiving docetaxel (HR 0.89; 95% CI 0.81,
0.98; P=0.02).
Addition of AATKIs to second line pemetrexed did not improve OS (HR 0.95; 95% CI 0.79, 1.13; P=0.54) nor in patients with squamous
histology (HR 1.01; 95% CI 0.87, 1.16; P=0.92).
Conclusion
The addition of AATKIs to chemotherapy in patients with advanced NSCLC prolongs OS, PFS and increases ORR, at the expense of increased
toxicity. Greatest benefit is in second line, in adenocarcinomas and in patients receiving docetaxel.
59. Background
Sunitinib is an oral, selective multi-targeted tyrosine kinase inhibitor (TKI) with antiangiogenic and antitumor
activities.
Evaluate the efficacy and toxicity of this therapeutic strategy.
Methods
Retrospective review of 30 stage IV NSCLC patients who received sunitinib as salvage therapy in Shanghai Chest
hospital, from January 2009 until August 2011.
All patients previously treated with EGFR-TKIs.
Results
Median PFS: 1.25 months (95% CI: 0.90-1.9 months).
Median OS: 3.40 months (95% CI: 3.00-6.80 months).
Of the 29 patients eligible for efficacy evaluation, none PR.
ECOG PS is predictive of both PFS (p=0.001) and OS (p<0.001).
Hand-foot syndrome (53.3%), mucositis (40.0%), rash (36.7%) and diarrhea (33.3%) most commonly reported
adverse events.
Conclusion
Sunitinib treatment did not demonstrate overall clinical benefits to the EGFR-TKI pretreated NSCLC Chinese
patients.
60. Background
Sunitinib is an oral, selective multi-targeted tyrosine kinase inhibitor (TKI) with antiangiogenic and antitumor
activities.
Evaluate the efficacy and toxicity of this therapeutic strategy.
Methods
Retrospective review of 30 stage IV NSCLC patients who received sunitinib as salvage therapy in Shanghai Chest
hospital, from January 2009 until August 2011.
All patients previously treated with EGFR-TKIs.
Results
Median PFS: 1.25 months (95% CI: 0.90-1.9 months).
Median OS: 3.40 months (95% CI: 3.00-6.80 months).
Of the 29 patients eligible for efficacy evaluation, none PR.
ECOG PS is predictive of both PFS (p=0.001) and OS (p<0.001).
Hand-foot syndrome (53.3%), mucositis (40.0%), rash (36.7%) and diarrhea (33.3%) most commonly reported
adverse events.
Conclusion
Sunitinib treatment did not demonstrate overall clinical benefits to the EGFR-TKI pretreated NSCLC Chinese
patients.
61. Background
Sorafenib as well as mTOR inhibitors showed preliminary activity in KRAS mutated NSCLC.
Methods
Patients with relapsed solid tumors.
Escalating doses of everolimus from 2.5-10.0 mg daily p.o. in a 14 days run-in phase Combination with a
fixed dose of sorafenib 400 mg bid p.o.
KRAS mutation status is determined by PCR based high resolution melting curve analysis (HRM) on DNA
extracted from FFPE material and validated using Sanger sequencing.
Results
19 patients were recruited. DLT was not reached.
MTD: 7.5 mg/day everolimus + 400 mg sorafenib.
The best treatment outcome on day 57 was stable disease in 11 patients.
Median PFS and OS were 3.7 and 5.5 months.
The extension phase in KRAS mutated NSCLC is currently ongoing.
Conclusion
Treatment of patients with relapsed solid tumors with the combination of 7.5 mg everolimus p.o. daily + 400
mg sorafenib p.o. bid is safe and feasible. Current results of an extension phase in KRAS mutated NSCLC
patients show preliminary clinical activity in this patient group with an unfavorable prognosis.
62. Background
Sorafenib as well as mTOR inhibitors showed preliminary activity in KRAS mutated NSCLC.
Methods
Patients with relapsed solid tumors.
Escalating doses of everolimus from 2.5-10.0 mg daily p.o. in a 14 days run-in phase Combination with a
fixed dose of sorafenib 400 mg bid p.o.
KRAS mutation status is determined by PCR based high resolution melting curve analysis (HRM) on DNA
extracted from FFPE material and validated using Sanger sequencing.
Results
19 patients were recruited. DLT was not reached.
MTD: 7.5 mg/day everolimus + 400 mg sorafenib.
The best treatment outcome on day 57 was stable disease in 11 patients.
Median PFS and OS were 3.7 and 5.5 months.
The extension phase in KRAS mutated NSCLC is currently ongoing.
Conclusion
Treatment of patients with relapsed solid tumors with the combination of 7.5 mg everolimus p.o. daily + 400
mg sorafenib p.o. bid is safe and feasible. Current results of an extension phase in KRAS mutated NSCLC
patients show preliminary clinical activity in this patient group with an unfavorable prognosis.
83. Background
Motesanib is an orally administrated small molecule antagonist of VEGFR 1, 2, 3, and platelet-derived growth factor receptor
(PDGFR), and stem cell factor receptor (c-kit).
Methods
Stage IV/recurrent non-squamous NSCLC patients without prior chemotherapy.
Oral motesanib (125 mg) or placebo once daily in combination with paclitaxel (200 mg/m2) and carboplatin (AUC = 6) every 3 weeks
up to 6 cycles and continue motesanib or placebo.
ECOG PS 0-1
400 patients will be randomized in a double-blind 1:1 ratio to motesanib or placebo.
Stratification factors: EGFR mutation status, weight loss of ≥ 5% in the previous 6 months, and region.
Results
First evaluation by IDMC performed using the data as of 26 December 2012.
63 patients (Japanese; median age, 64.5 y).
All the blinded patients who received study treatment experienced AEs.
Grade 3 to 5 AEs were reported in 38 patients (60.3%) Alopecia (63.5%), peripheral sensory neuropathy (57.1%), and decreased
appetite (50.8%).
7 patients had 8 serious AEs (SAEs) cholecystitis, gastric ulcer haemorrhage, nausea, and upper gastrointestinal hemorrhage
1 treatment-related fatal AE (interstitial lung disease)
Conclusion
The first IDMC recommended continuation of the study after the review of unblinded data of 63 patients.
Updated safety data will be presented after the second IDMC (JapicCTI-121887).