This document discusses a case of a 64-year-old man presenting with right flank pain and a history of smoking who is found to have clear-cell renal cell carcinoma (RCC). He undergoes a right radical nephrectomy and pathology confirms grade 3 clear-cell RCC without margins or lymph node involvement. Small lung nodules are detected 18 months later and biopsy confirms metastatic clear cell RCC. Systemic therapy options for the metastatic disease are discussed, including tyrosine kinase inhibitors, immunotherapy, and their combinations. Ongoing trials of immunotherapy in the adjuvant and metastatic settings are also summarized. Risk stratification models and their impact on treatment selection are reviewed.
High Through-Put DNA Methylation Analysis of Lung Cancer: Plasma cfDNA for Bi...Kate Barlow
• Technology pipeline for methylation biomarker
development
• High throughput DNA methylation-qPCR workflows
• Liquid biopsy – cfDNA methylation testing
The patient is a 64-year-old man who underwent radical nephrectomy 6 weeks prior for clear-cell renal cell carcinoma (RCC), stage T3aN0. He has no signs of disease recurrence but is at high risk. The document discusses whether adjuvant therapy is indicated and reviews recent phase 3 trials of adjuvant sunitinib versus placebo, which showed improved disease-free survival but not overall survival. It also reviews ongoing adjuvant immunotherapy trials versus placebo and optimal sequencing of systemic therapies if the cancer recurs.
This document summarizes Dr. Frederick Hagemeister's presentation on anti-PD-1 and anti-CD30 antibodies for Hodgkin lymphoma from the 2014 American Society of Hematology annual meeting. It discusses preliminary results from phase 1 trials of nivolumab and pembrolizumab for relapsed/refractory HL, as well as trials combining brentuximab vedotin with chemotherapy for untreated advanced HL. Response rates to anti-PD-1 antibodies were high across studies. Combining brentuximab vedotin with ABVD/AVD showed promising efficacy in untreated patients with acceptable toxicity.
Volker Diehl, M.D., Professor, University of Cologne, Germany Customization: The Treatment of Hodgkin's Disease
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Naiyer Rizvi, MD, and Benny Weksler, MBA, MD, prepared useful Practice Aids pertaining to lung cancer for this CME/MOC/CE activity titled "The Evolving Role of Immunotherapy as a Component of Multimodal Therapy in Earlier Stages of Lung Cancer: Rationale, Current Evidence, Key Trials, and Implications for Multidisciplinary Care." For the full presentation, monograph, complete CME/MOC/CE information, and to apply for credit, please visit us at http://bit.ly/2KEjDL6. CME/MOC/CE credit will be available until December 5, 2019.
This document summarizes a prospective, observational study evaluating the benefit and risk of the drug Vandetanib (Caprelsa) in patients with medullary thyroid cancer. The study will collect data from European patients who are RET mutation positive or negative and being treated with Vandetanib, as well as RET negative patients not receiving Vandetanib. The objectives are to assess response rates, disease control, progression-free survival, safety events, and other outcomes based on RET mutation status. Data will be collected from medical records and analyzed to compare outcomes between the groups.
High Through-Put DNA Methylation Analysis of Lung Cancer: Plasma cfDNA for Bi...Kate Barlow
• Technology pipeline for methylation biomarker
development
• High throughput DNA methylation-qPCR workflows
• Liquid biopsy – cfDNA methylation testing
The patient is a 64-year-old man who underwent radical nephrectomy 6 weeks prior for clear-cell renal cell carcinoma (RCC), stage T3aN0. He has no signs of disease recurrence but is at high risk. The document discusses whether adjuvant therapy is indicated and reviews recent phase 3 trials of adjuvant sunitinib versus placebo, which showed improved disease-free survival but not overall survival. It also reviews ongoing adjuvant immunotherapy trials versus placebo and optimal sequencing of systemic therapies if the cancer recurs.
This document summarizes Dr. Frederick Hagemeister's presentation on anti-PD-1 and anti-CD30 antibodies for Hodgkin lymphoma from the 2014 American Society of Hematology annual meeting. It discusses preliminary results from phase 1 trials of nivolumab and pembrolizumab for relapsed/refractory HL, as well as trials combining brentuximab vedotin with chemotherapy for untreated advanced HL. Response rates to anti-PD-1 antibodies were high across studies. Combining brentuximab vedotin with ABVD/AVD showed promising efficacy in untreated patients with acceptable toxicity.
Volker Diehl, M.D., Professor, University of Cologne, Germany Customization: The Treatment of Hodgkin's Disease
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Naiyer Rizvi, MD, and Benny Weksler, MBA, MD, prepared useful Practice Aids pertaining to lung cancer for this CME/MOC/CE activity titled "The Evolving Role of Immunotherapy as a Component of Multimodal Therapy in Earlier Stages of Lung Cancer: Rationale, Current Evidence, Key Trials, and Implications for Multidisciplinary Care." For the full presentation, monograph, complete CME/MOC/CE information, and to apply for credit, please visit us at http://bit.ly/2KEjDL6. CME/MOC/CE credit will be available until December 5, 2019.
This document summarizes a prospective, observational study evaluating the benefit and risk of the drug Vandetanib (Caprelsa) in patients with medullary thyroid cancer. The study will collect data from European patients who are RET mutation positive or negative and being treated with Vandetanib, as well as RET negative patients not receiving Vandetanib. The objectives are to assess response rates, disease control, progression-free survival, safety events, and other outcomes based on RET mutation status. Data will be collected from medical records and analyzed to compare outcomes between the groups.
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
CINV (chemotherapy induced nausea & vomiting)Mohamed Abdulla
This document discusses chemotherapy-induced nausea and vomiting (CINV). It provides background on the speaker's disclosures and affiliations. It then reviews the pathophysiology of CINV, risk factors, types of CINV, and the impact of inadequate CINV control on quality of life and treatment adherence. It discusses guidelines for preventing CINV and the efficacy of different antiemetic drugs, including 5-HT3 receptor antagonists, NK1 receptor antagonists, and steroids. It also reviews the evolution of CINV prevention over time with improved antiemetic regimens.
This document discusses urothelial carcinoma (UC), a type of bladder cancer. It provides statistics on UC in the US and India. Risk factors like smoking and occupational exposures are discussed. The drug Durvalumab is approved for treating advanced or metastatic UC. It works by blocking the PD-L1 protein, which inhibits the immune system's ability to fight cancer. Details are given on Durvalumab's mechanism of action, pharmacokinetics, dosage administration, storage, and common adverse reactions.
This document discusses the presentation, testing, and management of pituitary adenomas and hypothalamic syndromes. It provides guidance on testing a 66-year-old man with a confirmed pituitary adenoma discovered on MRI after presenting with stroke symptoms. Testing strategies and their limitations are reviewed. Factors affecting decisions around intervention and appropriate follow-up strategies are also discussed, drawing on literature to support recommendations. Long-term management of patients with prolactinomas on dopamine agonists is explored, including monitoring, treatment withdrawal, and surveillance of side effects.
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.
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.
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.
Robert Dreicer, MD, MS, MACP, FASCO, Michael S. Cookson, MD, MMHC, Oliver Sartor, MD, and Neal D. Shore, MD, FACS, prepared useful practice aids pertaining to prostate cancer management for this CME activity titled "Science and Stories: Navigating the Prostate Cancer Landscape - Urologists at the Intersection of Emerging Evidence and Patient Centric Care." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2JFhjpM. CME credit will be available until June 26, 2019.
This study examined predictors of contralateral breast cancer in unilateral breast cancer patients undergoing contralateral prophylactic mastectomy (CPM). The study analyzed 542 patients who underwent CPM at one cancer center between 2000-2007. Univariate analysis found that younger age, Gail risk score >1.67%, ipsilateral invasive lobular histology, additional ipsilateral moderate-high risk pathology, and multicentric ipsilateral tumor predicted higher risk of contralateral breast cancer. However, multivariate analysis identified only younger age and ipsilateral invasive lobular histology as independent predictors of contralateral breast cancer. The study aimed to help identify which unilateral breast cancer patients might most benefit from CPM.
Locally advanced and metastatic prostate cancer can be treated with surgery, radiation therapy, hormone therapy, chemotherapy, or a combination. For locally advanced disease, short-term and long-term hormone therapy combined with radiation therapy improves outcomes. Adjuvant radiation after prostatectomy improves survival for high-risk patients. Advanced disease is treated by depleting androgens through surgical or medical castration. Newer agents like abiraterone, enzalutamide, radium-223, cabazitaxel, and sipuleucel-T provide additional treatment options.
- Small cell lung cancer (SCLC) has seen little therapeutic advancement in over 20 years. Platinum-etoposide remains the standard chemotherapy regimen.
- For limited-stage SCLC, concurrent chemoradiation is the standard of care and provides better outcomes than sequential treatment. Early twice-daily radiotherapy with prophylactic cranial irradiation improves survival.
- For extensive-stage SCLC, prophylactic cranial irradiation after chemotherapy reduces the risk of brain metastases and improves survival compared to no cranial irradiation.
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.
New Directions in the Management of Relapsed/Refractory Follicular Lymphomai3 Health
This document provides clinical tools and resources for relapsed or refractory follicular lymphoma, including:
1) Grading and classification systems for follicular lymphoma, diagnostic testing procedures, and risk factors.
2) Potential treatment options for follicular lymphoma at initial diagnosis or relapse, including chemotherapy, immunotherapy, targeted therapy, and stem cell transplantation.
3) Recommended second-line treatment regimens for fit or frail adults with relapsed or refractory follicular lymphoma, including chemoimmunotherapy combinations and monoclonal antibodies.
This document summarizes several androgen receptor-targeted agents (apalutamide, enzalutamide, darolutamide) approved for treatment of prostate cancer, including their indications, dosing, and common adverse events. It also describes ongoing clinical trials evaluating these and other agents (PARP inhibitors, immunotherapy) alone or in combination for metastatic castration-sensitive, non-metastatic castration-resistant, and metastatic castration-resistant prostate cancer. Many trials are investigating these novel approaches in patients with DNA damage repair defects.
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.
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.
Edward B. Garon, MD, MS, Jamie E. Chaft, MD, and Matthew D. Hellmann, MD, prepared useful Practice Aids pertaining to lung cancer management for this CME/MOC/CE activity titled "Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Cancer Continuum: State of the Science and Implications for Practice." For the full presentation, monograph, complete CME/MOC/CE information, and to apply for credit, please visit us at http://bit.ly/2ATq0qp. CME/MOC/CE credit will be available until November 21, 2019.
This document discusses the treatment of low-grade gliomas. It notes that maximal surgical resection is generally recommended when feasible and associated with more favorable outcomes. For pilocytic astrocytomas, no adjuvant therapy is necessary after complete resection. Postoperative radiotherapy may be considered for incompletely resected or higher risk nonpilocytic gliomas. Recent trials found no survival advantage from higher radiation doses compared to 45-54 Gy or from early radiotherapy versus delayed radiotherapy. Temozolomide is being tested in clinical trials for nonpilocytic gliomas.
Journal club: Durvalumab as Consolidation therapy in Advanced NSCLCAnimesh Agrawal
This study evaluated the addition of durvalumab consolidation therapy following chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer. The study found that durvalumab improved progression-free survival compared to placebo, with median progression-free survival of 16.8 months versus 5.6 months respectively. Overall survival was also improved with durvalumab, though final analysis is still pending. Safety profiles were similar to other PD-L1 inhibitors, with immune-related adverse events in approximately 25% of durvalumab patients. This study provides evidence that durvalumab consolidation improves outcomes for stage III NSCLC following chemoradiotherapy.
This document outlines the treatment of advanced/metastatic renal cell carcinoma (RCC). It discusses that nephrectomy may still have a role in metastatic RCC for some patients. Active surveillance is an option for favorable risk metastatic RCC patients. Several trials found no differences between tyrosine kinase inhibitors as first line options for metastatic RCC. Second line options after progression on TKIs include mTOR inhibitors, VEGF inhibitors, and immune checkpoint inhibitors. Recent data supports immune checkpoint inhibitors like nivolumab plus ipilimumab as the new standard of care for first line treatment of metastatic RCC based on improved overall survival compared to sunitinib in clinical trials.
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
CINV (chemotherapy induced nausea & vomiting)Mohamed Abdulla
This document discusses chemotherapy-induced nausea and vomiting (CINV). It provides background on the speaker's disclosures and affiliations. It then reviews the pathophysiology of CINV, risk factors, types of CINV, and the impact of inadequate CINV control on quality of life and treatment adherence. It discusses guidelines for preventing CINV and the efficacy of different antiemetic drugs, including 5-HT3 receptor antagonists, NK1 receptor antagonists, and steroids. It also reviews the evolution of CINV prevention over time with improved antiemetic regimens.
This document discusses urothelial carcinoma (UC), a type of bladder cancer. It provides statistics on UC in the US and India. Risk factors like smoking and occupational exposures are discussed. The drug Durvalumab is approved for treating advanced or metastatic UC. It works by blocking the PD-L1 protein, which inhibits the immune system's ability to fight cancer. Details are given on Durvalumab's mechanism of action, pharmacokinetics, dosage administration, storage, and common adverse reactions.
This document discusses the presentation, testing, and management of pituitary adenomas and hypothalamic syndromes. It provides guidance on testing a 66-year-old man with a confirmed pituitary adenoma discovered on MRI after presenting with stroke symptoms. Testing strategies and their limitations are reviewed. Factors affecting decisions around intervention and appropriate follow-up strategies are also discussed, drawing on literature to support recommendations. Long-term management of patients with prolactinomas on dopamine agonists is explored, including monitoring, treatment withdrawal, and surveillance of side effects.
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.
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.
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.
Robert Dreicer, MD, MS, MACP, FASCO, Michael S. Cookson, MD, MMHC, Oliver Sartor, MD, and Neal D. Shore, MD, FACS, prepared useful practice aids pertaining to prostate cancer management for this CME activity titled "Science and Stories: Navigating the Prostate Cancer Landscape - Urologists at the Intersection of Emerging Evidence and Patient Centric Care." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2JFhjpM. CME credit will be available until June 26, 2019.
This study examined predictors of contralateral breast cancer in unilateral breast cancer patients undergoing contralateral prophylactic mastectomy (CPM). The study analyzed 542 patients who underwent CPM at one cancer center between 2000-2007. Univariate analysis found that younger age, Gail risk score >1.67%, ipsilateral invasive lobular histology, additional ipsilateral moderate-high risk pathology, and multicentric ipsilateral tumor predicted higher risk of contralateral breast cancer. However, multivariate analysis identified only younger age and ipsilateral invasive lobular histology as independent predictors of contralateral breast cancer. The study aimed to help identify which unilateral breast cancer patients might most benefit from CPM.
Locally advanced and metastatic prostate cancer can be treated with surgery, radiation therapy, hormone therapy, chemotherapy, or a combination. For locally advanced disease, short-term and long-term hormone therapy combined with radiation therapy improves outcomes. Adjuvant radiation after prostatectomy improves survival for high-risk patients. Advanced disease is treated by depleting androgens through surgical or medical castration. Newer agents like abiraterone, enzalutamide, radium-223, cabazitaxel, and sipuleucel-T provide additional treatment options.
- Small cell lung cancer (SCLC) has seen little therapeutic advancement in over 20 years. Platinum-etoposide remains the standard chemotherapy regimen.
- For limited-stage SCLC, concurrent chemoradiation is the standard of care and provides better outcomes than sequential treatment. Early twice-daily radiotherapy with prophylactic cranial irradiation improves survival.
- For extensive-stage SCLC, prophylactic cranial irradiation after chemotherapy reduces the risk of brain metastases and improves survival compared to no cranial irradiation.
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.
New Directions in the Management of Relapsed/Refractory Follicular Lymphomai3 Health
This document provides clinical tools and resources for relapsed or refractory follicular lymphoma, including:
1) Grading and classification systems for follicular lymphoma, diagnostic testing procedures, and risk factors.
2) Potential treatment options for follicular lymphoma at initial diagnosis or relapse, including chemotherapy, immunotherapy, targeted therapy, and stem cell transplantation.
3) Recommended second-line treatment regimens for fit or frail adults with relapsed or refractory follicular lymphoma, including chemoimmunotherapy combinations and monoclonal antibodies.
This document summarizes several androgen receptor-targeted agents (apalutamide, enzalutamide, darolutamide) approved for treatment of prostate cancer, including their indications, dosing, and common adverse events. It also describes ongoing clinical trials evaluating these and other agents (PARP inhibitors, immunotherapy) alone or in combination for metastatic castration-sensitive, non-metastatic castration-resistant, and metastatic castration-resistant prostate cancer. Many trials are investigating these novel approaches in patients with DNA damage repair defects.
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.
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.
Edward B. Garon, MD, MS, Jamie E. Chaft, MD, and Matthew D. Hellmann, MD, prepared useful Practice Aids pertaining to lung cancer management for this CME/MOC/CE activity titled "Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Cancer Continuum: State of the Science and Implications for Practice." For the full presentation, monograph, complete CME/MOC/CE information, and to apply for credit, please visit us at http://bit.ly/2ATq0qp. CME/MOC/CE credit will be available until November 21, 2019.
This document discusses the treatment of low-grade gliomas. It notes that maximal surgical resection is generally recommended when feasible and associated with more favorable outcomes. For pilocytic astrocytomas, no adjuvant therapy is necessary after complete resection. Postoperative radiotherapy may be considered for incompletely resected or higher risk nonpilocytic gliomas. Recent trials found no survival advantage from higher radiation doses compared to 45-54 Gy or from early radiotherapy versus delayed radiotherapy. Temozolomide is being tested in clinical trials for nonpilocytic gliomas.
Journal club: Durvalumab as Consolidation therapy in Advanced NSCLCAnimesh Agrawal
This study evaluated the addition of durvalumab consolidation therapy following chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer. The study found that durvalumab improved progression-free survival compared to placebo, with median progression-free survival of 16.8 months versus 5.6 months respectively. Overall survival was also improved with durvalumab, though final analysis is still pending. Safety profiles were similar to other PD-L1 inhibitors, with immune-related adverse events in approximately 25% of durvalumab patients. This study provides evidence that durvalumab consolidation improves outcomes for stage III NSCLC following chemoradiotherapy.
This document outlines the treatment of advanced/metastatic renal cell carcinoma (RCC). It discusses that nephrectomy may still have a role in metastatic RCC for some patients. Active surveillance is an option for favorable risk metastatic RCC patients. Several trials found no differences between tyrosine kinase inhibitors as first line options for metastatic RCC. Second line options after progression on TKIs include mTOR inhibitors, VEGF inhibitors, and immune checkpoint inhibitors. Recent data supports immune checkpoint inhibitors like nivolumab plus ipilimumab as the new standard of care for first line treatment of metastatic RCC based on improved overall survival compared to sunitinib in clinical trials.
This document summarizes information about immunotherapy for non-small cell lung cancer (NSCLC). It provides data on key clinical trials that evaluated immunotherapy drugs like nivolumab and pembrolizumab in previously treated NSCLC. It shows the efficacy results including overall survival benefits from these trials compared to chemotherapy. Long-term survival outcomes are also presented from pooled analyses of nivolumab trials with over 3 years of follow-up data.
Roy H. Decker, MD, PhD, and Sarah B. Goldberg, MD, MPH, prepared useful practice aids pertaining to lung cancer for this CME activity titled "The Era of Immunotherapy in Stage III NSCLC: Exploring the Evidence and Practicalities of Integrating Checkpoint Inhibition Into the Multimodal Treatment Arsenal." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2PU3iaZ. CME credit will be available until December 6, 2019.
This document discusses the challenges of providing radiation oncology care during the COVID-19 pandemic. It outlines various cancer patient groups that are most vulnerable to COVID-19 and the difficulties this poses for cancer treatment. Recommendations are provided for prioritizing patients and potentially altering treatment approaches, such as using hypofractionated regimens, for different cancer types including breast, lung, head and neck, and gynecological cancers. Guidance emphasizes continuing curative treatments when possible while considering safety and minimizing risks of virus exposure and spread.
El futuro del tratamiento del cáncer renal metastásico: inmunoterapia y terap...Mauricio Lema
Ponencia en el primer simposio de la Asociación Colombiana de Hematología y Oncología (ACHO) de cáncer genitourinario, Bogotá, septiembre 23 y 24 de 2016.
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MANAGEMENT OF EARLY STAGE NON SMALL CELL LUNG CARCINOMAIsha Jaiswal
1. The document discusses management guidelines for early stage non-small cell lung cancer (NSCLC), including treatment options for operable versus inoperable patients such as surgery, chemotherapy, and radiation therapy.
2. Key findings from studies on lymphadenectomy, sublobar resection versus lobectomy, and video-assisted thoracoscopic surgery (VATS) versus open surgery are summarized, finding no clear survival benefits to more extensive procedures in early stage disease.
3. The roles of postoperative radiotherapy and chemotherapy are examined based on clinical trials, with chemoradiation found potentially beneficial in stage III disease but not stage I/II, and cisplatin-based chemotherapy improving survival in stage II/III
Co-Chairs and Presenter Jessica Donington, MD, Jonathan D. Spicer, MD, PhD, FRCSC, and Patrick M. Forde, MD, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC/CC/AAPA activity titled “A Practical Guide for Making Multidisciplinary Decisions About Neoadjuvant and/or Adjuvant Immunotherapy in Resectable NSCLC.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/CC/AAPA information, and to apply for credit, please visit us at https://bit.ly/3MQVu5l. CME/MOC/CC/AAPA credit will be available until February 27, 2025.
1) The document discusses the evidence and guidelines for use of radiation therapy (RT) in treatment of low-grade glioma.
2) Several practice-changing randomized controlled trials showed that for high-risk low-grade glioma, combining RT and chemotherapy improved outcomes over RT alone.
3) For anaplastic glioma, combining RT and chemotherapy improved survival compared to RT alone, especially for those with 1p/19q co-deletion.
4) Ongoing trials are exploring whether initial observation may be reasonable for some low-grade glioma patients after surgery, versus early adjuvant treatment.
Has cancer science got you stumped and overwhelmed? Leading gynecologic oncologist, Dr. Don Dizon, takes us to cancer college in this webinar. He explains the science behind ovarian cancer, how it develops, how it's diagnosed, and how ovarian cancer treatments work.
This document summarizes new strategies for treating renal cancer and their impact on overall survival. It discusses several clinical trials that evaluated targeted therapies like sunitinib, sorafenib, bevacizumab, temsirolimus, everolimus, pazopanib, and axitinib. The selection of the appropriate treatment for each patient subgroup and line of therapy is key to improving patient overall survival. While targeted therapies have increased median progression-free survival and overall survival compared to cytokines, sequencing trials have been inconclusive and real-world outcomes lag behind clinical trials.
This document discusses recent updates in lung cancer. It begins by noting that lung cancer is the leading cause of cancer death in the US and is often diagnosed at an advanced stage. Screening with low-dose CT scans can detect lung cancer earlier and has been shown to decrease lung cancer mortality by 20% compared to chest x-rays. The National Lung Screening Trial established low-dose CT screening as an effective screening method for those at high risk. Biomarker testing is important to identify driver mutations and guide targeted therapy options, though barriers like tissue availability and turnaround time exist. Osimertinib has demonstrated superior progression-free survival compared to earlier EGFR TKIs for patients with EGFR-mut
The document provides information on managing adverse events associated with immune checkpoint inhibitors used to treat bladder cancer, including:
- A wide range of immune-related adverse events (irAEs) can occur affecting many organ systems such as the lungs, skin, gut, and endocrine system. irAEs are often diagnosed by excluding other causes and should be managed promptly.
- General recommendations for managing irAEs include monitoring for new symptoms, using corticosteroids for treatment, and potentially holding or discontinuing immunotherapy depending on severity. Most patients recover from irAEs with appropriate treatment.
- Specific guidance is provided on managing different grade levels (1-4) of irAEs, including using high-
1. Small cell lung carcinoma is a highly aggressive malignancy associated with tobacco exposure. It is characterized pathologically by small, round, blue cells with scant cytoplasm and fine chromatin.
2. Prognostic factors include stage, performance status, gender, and normal LDH levels. Staging workup involves imaging of the chest, abdomen, brain and bone as well as biopsy of suspicious lesions.
3. Treatment depends on stage - limited stage receives chemotherapy with thoracic radiation while extensive stage receives chemotherapy alone with consideration of prophylactic cranial irradiation for those who respond to initial treatment. The standard chemotherapy regimen is etoposide and platinum.
This document provides a summary of a clinical presentation on advances in the treatment of head and neck cancer. The presentation was given by four experts and discussed topics such as the prognostic value of tumor-infiltrating lymphocytes in head and neck squamous cell carcinoma, PD-L1 expression and outcomes with PD-1/PD-L1 inhibitors, ongoing immunotherapy trials, immune-related adverse events, TRK fusions found across cancer types, methods for detecting TRK fusions, and efficacy of TRK inhibitors.
This randomized controlled trial compared preoperative chemoradiotherapy to immediate surgery for resectable or borderline resectable pancreatic cancer. It found no significant difference in overall survival between the two groups based on intention-to-treat analysis. However, the preoperative chemoradiotherapy group had higher R0 resection rates and more favorable pathological outcomes. Compliance with preoperative treatment was also better. For borderline resectable disease specifically, preoperative chemoradiotherapy showed a prolonged overall survival compared to immediate surgery.
This document reviews treatments for neuroendocrine tumors (NETs), including peptide receptor radionuclide therapy (PRRT). It summarizes the evidence for various NET treatment options such as surgery, somatostatin analogs, PRRT, chemotherapy, and targeted therapies. It also provides an overview of a PRRT treatment day and integrates PRRT with other NET therapies. Clinical trial data is presented demonstrating the efficacy of PRRT and targeted therapies such as everolimus and sunitinib in extending progression-free survival for NETs. The conclusion emphasizes treating NETs only when necessary and considering surgery first followed by somatostatin analogs, PRRT, intra-arterial therapies,
This document discusses biomarkers in cancer immunotherapy. It begins by defining an immuno-biomarker as a measurable indicator of the immune system's response to cancer or its treatment. Biomarkers can be used to predict response, resistance, toxicity, and hyperprogression to immunotherapy. Popular biomarkers discussed include PD-L1 expression, tumor mutational burden (TMB), and T-cell receptor (TCR) repertoire. The predictive value of these biomarkers is explored for various cancer types. Limitations and heterogeneity of PD-L1 expression are also noted. The document examines ongoing efforts to standardize the measurement and clinical application of biomarkers to optimize immunotherapy.
This document provides a pathology report for a 34-year-old female patient. It summarizes the findings from biopsies of the right and left breast. For the right breast, it finds an invasive ductal carcinoma measuring 1.5 x 1.3 x 1 cm. Three of 39 lymph nodes from the right axilla showed metastatic carcinoma. The left breast tissue showed benign findings with no evidence of malignancy. The conclusion is infiltrating ductal carcinoma of the right breast with metastasis to 3 lymph nodes, classified as T1c/N1a.
The document discusses several antibody-drug conjugates (ADCs) that are being studied or developed for the treatment of non-small cell lung cancer (NSCLC). It summarizes clinical trial results of trastuzumab emtansine and trastuzumab deruxtecan for HER2-positive NSCLC, and sacituzumab govitecan and datopotamab deruxtecan for Trop-2 positive NSCLC. It also briefly mentions ADCs in development that target HER3, c-MET, CEACAM5, Axl, PTK7, NaPi2b, and Nectin-4 for lung cancer. The document concludes by reviewing a phase 1 clinical trial of
Indian women are more likely to have certain types of cancer according to Dr. R. Rajkumar. Over the last 25 years, large cancer trials have led to better outcomes for patients. Current research focuses on understanding cancer genes and cell growth to develop more targeted individualized treatments.
This document discusses treatment options for triple negative breast cancer (TNBC). It begins with a case study of a 56-year-old female patient diagnosed with TNBC. It then provides details on the characteristics and subtypes of TNBC, noting that it is an aggressive disease with poor prognosis. Current treatment approaches for metastatic TNBC are discussed, including sequential single-agent chemotherapy with taxanes, anthracyclines, antimetabolites, and platinum agents. Several key clinical trials comparing different chemotherapy regimens for TNBC are summarized, such as the TNT trial comparing carboplatin and docetaxel, and the TNACITY trial evaluating nab-paclitaxel plus carboplatin
This document provides guidelines for the management of gestational trophoblastic neoplasia (GTN). It outlines recommendations for initial treatment, monitoring, diagnosis of persistent postmolar GTN, and treatment approaches depending on the risk level and response. For low-risk GTN, single-agent chemotherapy such as methotrexate or dactinomycin is recommended. For high-risk or relapsed GTN, more intensive regimens including EMA/CO are used. Treatment is monitored closely with hCG assays and adjusted based on the tumor response.
The OUTBACK trial compared standard chemoradiation (CRT) to CRT plus adjuvant carboplatin and paclitaxel (ACT) in patients with locally advanced cervical cancer. Over 900 patients were randomized 1:1 to receive either CRT alone or CRT followed by ACT. Baseline characteristics were well balanced between the two arms. The primary endpoint was overall survival and secondary endpoints included progression-free survival, adverse events, sites of recurrence, and patient-reported outcomes.
This document discusses a clinical case presentation of a patient with metastatic renal cell carcinoma (mRCC). Key details include that the patient previously underwent nephrectomy and radiation therapy and is now being discussed for systemic therapy options. The document reviews several clinical trials evaluating different combination regimens for first-line and subsequent lines of treatment in mRCC. Factors like prognostic risk categories and biomarkers are discussed for guiding treatment selection. The merits and limitations of different studies are evaluated.
Here are a few key points regarding carfilzomib-associated cardiac adverse events based on clinical trial data:
- CHF and hypertension are the most common cardiac AEs seen with carfilzomib. Rates are generally higher than with bortezomib or lenalidomide doublets.
- Hypertension can usually be managed medically with antihypertensives like ACE inhibitors. Close monitoring of BP is important.
- Risk factors for cardiac AEs include older age, prior cardiac history, diabetes, renal dysfunction. However, events can still occur in lower risk patients.
- No definitive biomarkers yet to reliably predict risk. Troponin elevation during treatment may indicate higher risk but
Metronomic chemotherapy involves administering lower doses of chemotherapy drugs more frequently to target tumor growth. This summary approach has three potential mechanisms of action - inhibiting angiogenesis, stimulating the immune system, and directly targeting tumor cells. It yields long-term improved outcomes despite slower initial decreases in tumor size compared to maximum tolerated dose regimens. Clinical trials have shown metronomic chemotherapy to be an effective treatment approach in several cancer types including breast, colon, ovarian and prostate cancer when used as a single agent or in combinations.
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.
- The patient is a 36-year-old man who underwent neoadjuvant chemoradiotherapy in 2015 for rectal cancer.
- In 2021, he presented with frequent urination. Imaging showed a large recurrent mass involving abdominal structures.
- Biopsy of the skin deposit was suspicious for metastatic mucinous carcinoma.
- The case discusses the current treatment approaches for locally advanced rectal cancer, including neoadjuvant and total neoadjuvant therapy options, and choices for chemotherapy and radiotherapy.
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
This presentation discusses breast cancer, specifically hormone receptor positive/HER2 negative breast cancer. It provides statistics on the distribution of breast cancer molecular subtypes in the United States. It also discusses the evolving treatment landscape for hormone receptor positive metastatic breast cancer, including the approvals and use of targeted therapies in combination with endocrine therapy, such as CDK4/6 inhibitors. Clinical trial results are summarized that demonstrate improved progression-free survival when a CDK4/6 inhibitor is added to first-line endocrine therapy for advanced hormone receptor positive breast cancer. An approach to personalized therapy is proposed based on factors such as endocrine sensitivity and molecular alterations.
Cervical cancer is the second most common cancer in women worldwide. Over 500,000 women die from cervical cancer each year, most in low- and middle-income countries. The document discusses the epidemiology, risk factors, symptoms, diagnosis, staging, treatment, and prevention of cervical cancer. Screening and HPV vaccination can prevent cervical cancer but coverage is still low in India.
Case discussion ovarian cancer (nx power lite copy)madurai
This document discusses a case report from Dr. R. Rajkumar regarding genetic testing results for a 55-year-old female patient. Genetic testing of the patient's sample using next generation sequencing did not detect any deleterious mutations in the BRCA1 or BRCA2 genes. The report provides background information on BRCA gene mutations and their association with breast and ovarian cancer risk. It also discusses the role of homologous recombination repair and how mutations in genes involved in this pathway can lead to homologous recombination deficiency.
- 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
This document summarizes a tumor board discussion of a case involving a 21-year-old patient presenting with loose stools and abdominal pain for 2 months. Key details include KRAS mutation testing of the patient's tumor sample, which showed no mutation. The discussion covers epidemiology of early-onset colorectal cancer in India, treatment options including chemotherapy and targeted therapies, and factors influencing first-line treatment decisions for metastatic colorectal cancer such as biomarker status and primary tumor location.
This document discusses recent updates in treating metastatic colorectal cancers. It presents several case studies of patients diagnosed with colorectal cancer and large metastatic tumors. It then reviews the epidemiology of colorectal cancer in India, including rising incidence rates. The document outlines different classifications and treatment approaches for patients with metastatic disease, including the goal of increasing overall survival. It also discusses the increasing number of treatment options and challenges of personalizing therapy based on a patient's molecular profile.
This document discusses genetic testing for breast and ovarian cancer risk. It notes that not everyone with breast cancer needs genetic testing, but certain high-risk groups should be referred for further evaluation, such as those diagnosed at a young age or with a family history. Genetic testing can find pathogenic mutations that increase cancer risk or identify variants of uncertain significance. A positive test result indicates increased cancer risks and screening/prevention options, while a negative result does not rule out hereditary risk based on personal/family history factors. Over time, the rate of uncertain variants from BRCA1/2 testing has declined as knowledge improves. Most breast cancers still do not have an identifiable inherited genetic mutation.
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
- 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
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
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.
2. CASE DISCUSSION
• 64-yr-old man presents with right flank pain, no hematuria
• Past medical history includes:
• Mild hypertension (140/85 mmHg, not on medication),
hypercholesterolemia, no other cardiac history
• 20 pack-yr smoker
• Family history: negative for cancer
• Physical exam: right flank fullness, otherwise normal
• ECOG PS 0
• Labs: hemoglobin: 11.0 g/dL, ANC and platelets normal,
creatinine: 1.2 mg/dL, LDH: 287 U/L, calcium normal
5. WHAT IS THE NEXT STEP FOR THIS
PATIENT ?
1. Radical Nephrectomy
2. Start Systemic therapy
6. CASE DISCUSSION
• Patient undergoes right
radical nephrectomy
• Pathology: grade 3 clear-
cell RCC; margins negative;
T3aN0
• Returns 6 wks after
nephrectomy; fully
recovered
• ECOG PS 0, creatinine 1.5
mg/dL; all other labs
normal
7. WHAT IS ROLE OF ADJUVANT THERAPY
IN THIS PATIENT..?
ADJUVANT THERAPY INDICATED
NO EVIDENCE
EQUIVOCAL
8. S-TRAC PHASE III TRIAL: DFS WITH SUNITINIB VS PLACEBO
IN PATIENTS WITH LOCOREGIONAL, HIGH-RISK CCRCC
51.3%
59.5%
5-yr
DFS rate: Median DFS, Yrs (95% CI)
Sunitinib 6.8 (5.8-NR)
Placebo 5.6 (3.8-6.6)
Yrs
HR: 0.761 (95% CI: 0.594-0.975)
2-sided log-rank P = .030 stratified by UISS high-risk group
3-yr
DFS rate:
64.9%
59.3%
1.0
0.8
0.6
0.4
0.2
0
0 1 2 3 4 5 6 7 8 9
Patients at Risk, n
Sunitinib
Placebo
309
306
225
220
173
181
153
150
144
135
119
102
53
37
10
10
3
2
0
0
Proportion
Disease
Free
9. PUBLISHED TYROSINE KINASE INHIBITOR
ADJUVANT TRIALS
Trial Therapy N Histology Stage
Starting
Dose
Minimum
Dose
DFS OS
ASSURE[1] Sunitinib
Sorafenib
Placebo
1943 79% ccRCC
> pT1b, G3-4,
or N+
50 or 37.5
mg (Su)/
400 mg
(So)
25 mg
(Su)/40 mg
(So)
No No
S-TRAC[2] Sunitinib
Placebo
615 ccRCC > pT3b or N+ 50 mg 37.5 mg Yes No
PROTECT[3] Pazopanib
Placebo
1538
ccRCC or
mostly
ccRCC
pT2 (G3-4), ≥
pT3, or N+
600 mg 400 mg No No
10. ONGOING PHASE III ADJUVANT TRIALS:
IMMUNOTHERAPY VS PLACEBO
Parameter
IMmotion010[1]
(NCT03024996)
PROSPER[2] (NCT03055013)
KEYNOTE-564[3]
(NCT03142334)
CheckMate 914[4]
(NCT03138512)
Drug Atezolizumab Nivolumab Pembrolizumab Nivolumab + ipilimumab
Histology
Clear-cell ± sarcomatoid
histology
RCC of any histology
Clear-cell ± sarcomatoid
features
Clear-cell ± sarcomatoid
features
Dose duration 1 yr
2 doses prior to surgery and
adjuvant nivolumab for 9
mos
1 yr 6 mos
Risk
classification
T2 grade 4, T3a grade 3/4,
T3b/c any grade, T4 any grade,
or TxN+ any grade
Clinical stage ≥ T2 or
any N+
pT2, grade 4; pT3/4, any
grade; N+ M0; M1 NED
pT2aN0, grade 3-4; pT2b-T4;
N+
Primary
endpoint
DFS RFS at 5 yrs DFS DFS
BICR Yes Yes Yes Yes
Status Active, recruiting Active, recruiting Active, recruiting Active, recruiting
1.
11. CASE DISCUSSION
CT scans first reveal small,
indeterminate lung nodules
approximately 18 mos after
surgery
12. CASE DISCUSSION
Patient undergoes a lung biopsy,
further progression of lung lesions and
development of mediastinal lymph
node involvement
Pathology consistent with clear-cell RCC
ECOG PS 0
Lab results are all within normal limits
The patient has mild HTN controlled
with amlodipine
Favorable risk per IMDC criteria
13. Do you do risk stratification of your patients
in clinical practice..?
If Yes, which one do you prefer
‒ IMDC
‒ MSKCC
14. WHAT ARE THE PROGNOSTIC
INDICATORS IN mRCC DO YOU
CONSIDER WHILE CHOOSING THE
TREATMENT OPTIONS ?
20. During AS, the best overall responses were stable disease for 48 patients (83 %) and progressive disease (PD) for 10 patients (17 %), and 47 patients
With a median follow-up of 31.4 months, the
median TTP was 12.4 months (95 % confidence interval
8.4–16.5) and median overall survival was not reached
Karnofsky performance status <100 %, liver metastasis, and a time from diagnosis to AS of less
than 1 year were found to be predictive factors for a shorter TTP
29. CheckMate 214: OS and Response by IMDC Risk
Category
Tannir. ASCO GU 2020. Abstr 609. Slide credit: clinicaloptions.com
OS in Intermediate-Risk and Poor-Risk Patients OS in Favorable-Risk Patients
Nivolumab + ipilimumab (n = 425)
Sunitinib (n = 422)
Outcome in
Favorable-Risk Patients
Nivolumab + Ipilimumab
(n = 125)
Sunitinib
(n = 124)
HR (95% CI) P Value
ORR, % (95% CI) 29 54 -- < .0001
Median PFS, mos (95% CI) 17.8 (10.3-20.7) 27.7 (23.2-34.5) 1.62 (1.14-2.32) < .01
100
80
60
40
20
0
OS
(%)
0 3 6 9 12151821242730333639424548515457
60%
47%
39%
74%
60%
52%
HR: 0.66 (95% CI: 0.55-0.80; P < .0001)
Mos
70%
100
80
60
40
20
0
OS
(%)
0 3 6 9 12151821242730333639424548515457
Mos
88%
80%
93%
85%
73%
Nivolumab + ipilimumab (n = 125)
Sunitinib (n = 124)
HR: 1.19 (95% CI: 0.77-1.85; P = .44)
30. KEYNOTE-426: OS, PFS, and ORR in
IMDC Favorable-Risk Group
OS
HR: 1.06 (95% CI: 0.60-1.86)
PFS
HR: 0.76 (95% CI: 0.57-1.09)
Mos
Patients
at Risk, n
P + A
S
Plimack. ASCO 2020. Abstr 5001.
ORR
(%)
ORR
69.6% vs 50.4%
Pembro + Axi Sunitinib
11% CR
6% CR
CR
PR
100
90
80
70
60
50
40
30
20
10
0
OS
(%)
100
90
80
70
60
50
40
30
20
10
0
85%
88%
Events, n Median
26 NR
24 NR
42
0 6 12 18 24 30 36
138
131
134
129
131
123
126
118
110
108
63
60
12
9
0
0
*Nominal P value.
Mos
PFS
(%)
100
90
80
70
60
50
30
20
10
0
45%
42
0 6 12 18 24 30 36
138
131
111
99
88
66
67
46
41
26
13
8
0
0
0
0
Events, n
77
75
Median, Mos
(95% CI)
20.8 (15.4-28.8)
18.0 (12.5-20.8)
40
35%
31.
32. First-Line Treatment Considerations for RCC: Summary
Multiple good systemic therapy options for metastatic RCC, with no obvious
clear choice in some cases
Good-risk patients, and those with “favorable intermediate” risk, can have
survival of many yrs—with and without therapy
Consider debulking nephrectomy and/or active surveillance in selected patients
Patients with:
• IMDC intermediate/poor-risk
disease
• No significant autoimmune
disease
• VEGF contraindications
• A need to avoid chronic
VEGF AEs
Consider
Nivo + Ipi
Patients with
• IMDC favorable- or
intermediate-risk disease
• Intermediate- or poor- risk
disease who need rapid
response
• A need to avoid irAEs associated
with dual IO therapy
Consider
Pembro +
Axitinib
45. Considerations for Next-Line Treatment Selection
If disease control > 1 yr on first-line single-agent VEGF inhibitor, continue VEGF
inhibition with sequential single agents: such as Cabozantinib or Axitinib
If brief response to single-agent VEGF inhibition, consider a VEGF IO combination:
Axitinib + Pembrolizumab (based on Lenvatinib + Pembro data)
If no response to first-line VEGF inhibition, drop VEGF and switch to
immunotherapy: Ipilimumab + Nivolumab or Nivolumab
If no response to combination VEGF + IO switch to second line VEGF such as
Cabozantinib or Axitinib or Lenvatinib + Everolimus
‒ Phase III data support sequential VEGF therapy
‒ Limited data to support sequential IO therapy
46. WHEN WOULD YOU PREFER THE LENVATINIB +
EVEROLIMUS COMBINATION IN THE
MANAGEMENT OF mRCC?
47. STUDY 205: A RANDOMISED, PHASE 2,
OPEN-LABEL, MULTICENTRE TRIAL
aRCC: advanced renal cell carcinoma, Ca: calcium, ECOG: Eastern Cooperative Oncology Group, Hb: haemoglobin, IRR: independent radiological review, mmHg: millimeter of mercury, mRCC: metastatic renal cell carcinoma, ORR: objective response
rate, OS: overall survival, PFS: progression-free survival, RCC: renal cell carcinoma, RECIST: Response Evaluation Criteria in Solid Tumours, VEGF: vascular endothelial growth factor.
1. Motzer RJ et al. Lancet Oncol 2015;16(15):1473‒1482.
Key Eligibility Criteria:
• Histologically verified clear-cell RCC
• Radiographic evidence of progressive aRCC or mRCC
within 9 months of stopping previous treatment
• 1 previous disease progression with VEGF treatment
• ECOG PS 0 or 1
• Measurable disease per RECIST v1.1
• ≤ 150/90 mmHg blood pressure
• Adequate renal, bone marrow, blood coagulation, liver
and cardiac function
Stratification Factors:
• Hb
(Men: ≤130 g/L and >130 g/L, Women: ≤115 g/L
and >115 g/L)
• Corrected serum Ca
(≥2.5 mmol/L and <2.5 mmol/L)
End Points:
• Primary: PFS
• Key secondary: ORR, OS and safety
18 mg lenvatinib plus 5 mg everolimus
Once per day
10 mg everolimus monotherapy
Once per day
R
(1:1:1)
24 mg lenvatinib monotherapy
Once per day
n = 51
n = 50
n = 52
48. PRIMARY ENDPOINT – PROGRESSION-FREE
SURVIVAL
CI: confidence interval, HR: hazard ratio.
1. Motzer RJ et al. Lancet Oncol 2015;16(15):1473‒1482.
PFS was significantly
prolonged with
lenvatinib plus
everolimus, compared
with everolimus alone
(p=0.0005)1
• Approximately 9
additional months of
PFS benefit1
• 60% reduction in the
risk of
progression or death1
49. SECONDARY ENDPOINT – ORR
Assessed by Investigator review per RECIST v1.1
CI.
Lenvatinib plus
everolimus
(n=51)
Lenvatinib
monotherapy
(n=52)
Everolimus
monotherapy
(n=50)
OBJECTIVE RESPONSE
Events 22 (43%) 14 (27%) 3 (6%)
95% CI 29–58 16–41 1–17
Best overall response
Complete
response
1 (2%) 0 0
Partial response 21 (41%) 14 (27%) 3 (6%)
Stable disease 21 (41%) 27 (52%) 31 (62%)
Progressive
disease
2 (4%) 3 (6%) 12 (24%)
Not assessed 6 (12%) 8 (15%) 4 (8%)
43% ORR
for lenvatinib plus
everolimus vs 6% with
everolimus alone
(rate ratio [RR] 7·2, 95% CI:
2·3–22·5; p<0·0001)1
Lenvatinib plus everolimus
• Duration of response was
13.0 months1
• Time to response was 1.9
months2
50. SECONDARY ENDPOINT – ORR
Treatment Group:
Lenvatinib 18 mg plus Everolimus 5 mg
Treatment Group:
Lenvatinib 24 mg
Treatment Group:
Everolimus 10 mg
Figure S1. Maximum percentage change in sum of diameters of target lesions, for A) lenvatinib/everolimus combination arm, B) lenvatinib , and C) everolimus.
More patients in the lenvatinib plus everolimus group experienced measurable tumour shrinkage vs
those treated with everolimus alone