The document discusses the importance of molecular testing in advanced non-small cell lung cancer (NSCLC) to identify subsets of patients that may benefit from targeted therapies. It summarizes several studies that showed significantly improved outcomes with EGFR tyrosine kinase inhibitors compared to chemotherapy in patients with EGFR mutations. Additionally, KRAS mutations were found to confer resistance to EGFR inhibitors in NSCLC.
There are promising new agents coming to treat colorectal cancer, including biomarkers to guide treatment selection, targeted therapies, immunotherapy, and new ways to deliver chemotherapy and targeted therapies. Specifically, targeted therapies work by targeting molecular pathways involved in cancer development and survival. Biomarkers like KRAS, BRAF, and EGFR help determine which targeted therapies may work best. Immunotherapy and combinations of targeted agents and chemotherapy also show promise. Molecular profiling of tumors is helping to better understand colorectal cancer subtypes and identify new treatment opportunities.
1) A trial found that adding bevacizumab to chemotherapy for stage III colon cancer extended disease-free survival compared to chemotherapy alone, delaying cancer relapse but not preventing it completely.
2) There was no overall survival benefit observed from adding bevacizumab, suggesting it delays but does not alter the underlying biology of the disease.
3) The interpretation is that relapses were delayed by bevacizumab treatment but then occurred at a steady rate later on, similar to the chemotherapy alone group.
This document summarizes new targeted therapies for non-small cell lung cancers (NSCLCs). It discusses targeted agents for driver mutations in adenocarcinomas, including crizotinib for ALK rearrangements and ROS1 fusions, selective EGFR inhibitors, and investigational therapies targeting KRAS, BRAF, HER2 and MET alterations. Crizotinib improves outcomes over chemotherapy for ALK-positive NSCLC. Second generation ALK and EGFR inhibitors show responses in patients resistant to first-line therapies. The document also briefly mentions targeted approaches for squamous cell carcinomas but notes driver mutations are less common in this histology.
This document provides an overview and preliminary assessment of AstraZeneca's oncology portfolio. It summarizes their current approved oncology drugs, key disease areas and scientific platforms. It also outlines their extensive clinical development pipeline, with 13 late-stage programs, 17 phase 3 programs, 10 phase 2 programs and 26 phase 1 programs. Many of these programs are expected to file for approval in late 2016 and 2017, creating significant commercialization opportunities but also resource requirements to optimize launches. The oncology landscape is highly competitive, especially in AstraZeneca's core areas, and will continue expanding with new treatment classes.
This document summarizes the evolution of systemic therapy for non-small cell lung cancer (NSCLC) from empiric chemotherapy to molecularly-driven approaches. It discusses:
1) How histological classification is now necessary for treatment decisions, as different chemotherapy regimens have different efficacy depending on adenocarcinoma or squamous cell carcinoma subtype.
2) How maintenance therapy and extended duration of therapy have shown survival benefits compared to stopping treatment after a set number of cycles.
3) The need for molecular classification of NSCLC to guide targeted therapies, including determining EGFR and ALK status to select appropriate first-line tyrosine kinase inhibitors or chemotherapy. Ongoing research aims to identify more driver mutations
There are promising new agents coming to treat colorectal cancer, including biomarkers to guide treatment selection, targeted therapies, immunotherapy, and new ways to deliver chemotherapy and targeted therapies. Specifically, targeted therapies work by targeting molecular pathways involved in cancer development and survival. Biomarkers like KRAS, BRAF, and EGFR help determine which targeted therapies may work best. Immunotherapy and combinations of targeted agents and chemotherapy also show promise. Molecular profiling of tumors is helping to better understand colorectal cancer subtypes and identify new treatment opportunities.
1) A trial found that adding bevacizumab to chemotherapy for stage III colon cancer extended disease-free survival compared to chemotherapy alone, delaying cancer relapse but not preventing it completely.
2) There was no overall survival benefit observed from adding bevacizumab, suggesting it delays but does not alter the underlying biology of the disease.
3) The interpretation is that relapses were delayed by bevacizumab treatment but then occurred at a steady rate later on, similar to the chemotherapy alone group.
This document summarizes new targeted therapies for non-small cell lung cancers (NSCLCs). It discusses targeted agents for driver mutations in adenocarcinomas, including crizotinib for ALK rearrangements and ROS1 fusions, selective EGFR inhibitors, and investigational therapies targeting KRAS, BRAF, HER2 and MET alterations. Crizotinib improves outcomes over chemotherapy for ALK-positive NSCLC. Second generation ALK and EGFR inhibitors show responses in patients resistant to first-line therapies. The document also briefly mentions targeted approaches for squamous cell carcinomas but notes driver mutations are less common in this histology.
This document provides an overview and preliminary assessment of AstraZeneca's oncology portfolio. It summarizes their current approved oncology drugs, key disease areas and scientific platforms. It also outlines their extensive clinical development pipeline, with 13 late-stage programs, 17 phase 3 programs, 10 phase 2 programs and 26 phase 1 programs. Many of these programs are expected to file for approval in late 2016 and 2017, creating significant commercialization opportunities but also resource requirements to optimize launches. The oncology landscape is highly competitive, especially in AstraZeneca's core areas, and will continue expanding with new treatment classes.
This document summarizes the evolution of systemic therapy for non-small cell lung cancer (NSCLC) from empiric chemotherapy to molecularly-driven approaches. It discusses:
1) How histological classification is now necessary for treatment decisions, as different chemotherapy regimens have different efficacy depending on adenocarcinoma or squamous cell carcinoma subtype.
2) How maintenance therapy and extended duration of therapy have shown survival benefits compared to stopping treatment after a set number of cycles.
3) The need for molecular classification of NSCLC to guide targeted therapies, including determining EGFR and ALK status to select appropriate first-line tyrosine kinase inhibitors or chemotherapy. Ongoing research aims to identify more driver mutations
1) EGFR mutations are found in 10-30% of NSCLC cases and are associated with response to EGFR TKIs as first-line treatment.
2) Several studies including IPASS, EURTAC and LUX-Lung 3 have shown superior PFS for first-generation EGFR TKIs like gefitinib and erlotinib and the second-generation TKI afatinib compared to platinum-based chemotherapy as first-line treatment for EGFR mutation-positive NSCLC.
3) Meta-analyses of these studies demonstrate improved PFS for EGFR TKIs compared to chemotherapy in EGFR mutation-positive NSCLC, though OS is generally similar between the treatments
This document discusses evolving strategies for the personalized treatment of non-small cell lung cancer (NSCLC). It covers histological and molecular subtypes of NSCLC, key clinical trials of the EGFR tyrosine kinase inhibitor gefitinib, mechanisms of acquired resistance to EGFR TKIs, and approaches to managing resistance. A phase IV study showed gefitinib was effective first-line therapy for Caucasian patients with EGFR mutation-positive NSCLC, with a 69.8% response rate and favorable progression-free and overall survival. Exploratory analyses found plasma samples could accurately assess EGFR mutation status when tumor tissue was unavailable. The document reviews strategies for treating systemic and central nervous system progression after acquiring resistance to EGFR T
Treatment of Non–Small-Cell Lung Cancer with Erlotinib or Gefitinibseayat1103
This document discusses a clinical trial comparing the efficacy of erlotinib and gefitinib for the treatment of non-small cell lung cancer. The trial found that both erlotinib and gefitinib showed efficacy in NSCLC patients with EGFR mutations, with erlotinib demonstrating a median progression-free survival of 10.8 months compared to 5.4 months for standard chemotherapy in EGFR mutation-positive patients. Subsequent studies confirmed the superior efficacy of both erlotinib and gefitinib in NSCLC patients with EGFR mutations, particularly those with exon 19 deletions or L858R mutations. The document concludes by discussing the current NCCN guidelines for use of erlotinib and
New developments of targeted therapy in nsclclihua jiao
Targeted therapies have improved outcomes for patients with lung cancer harboring specific mutations. Several studies showed first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) improved response rates and progression-free survival over chemotherapy for patients with EGFR mutations. Resistance often emerges due to the T790M mutation. Irreversible EGFR TKIs like afatinib have shown activity against T790M resistance. Crizotinib demonstrated high response rates and prolonged progression-free survival in patients with anaplastic lymphoma kinase (ALK) rearrangements. New ALK inhibitors are in development. Selumetinib, a MEK inhibitor, showed clinical benefit in patients with KRAS mutations
Geoffrey Oxnard, MD, discusses the latest research in targeted therapies and molecular testing to treat lung cancer.
This presentation was originally given as part of "Living with Lung Cancer: A Forum for Patients and Caregivers" on Nov. 14, 2015 at Dana-Farber Cancer Institute in Boston, Mass.
The document summarizes clinical updates and advances in the treatment of non-small cell lung cancer (NSCLC). It discusses the incidence, subtypes and staging of NSCLC and recommendations for adjuvant therapy, targeted therapy and treatment of metastatic disease. It also reviews results from randomized trials of adjuvant chemotherapy showing improved survival compared to observation alone.
1. Receptor tyrosine kinases (RTKs) drive key cancer pathways and can be exploited as therapeutic targets, as shown by drugs like imatinib that inhibit mutated kinases in cancers.
2. RTK inhibitors have shown efficacy against cancers dependent on single kinases, but resistance often emerges through secondary mutations or bypass pathways.
3. Effective combination therapies are needed to overcome resistance, such as combining RTK inhibitors with other drugs that block downstream or bypass pathways.
- Non-small cell lung cancer is the most common malignancy worldwide and a leading cause of cancer death. It accounts for the majority (70-80%) of lung cancers.
- Imaging techniques like CT scans are important for accurately assessing the primary tumor and detecting metastasis. Positron emission tomography (PET) CT is more sensitive than size-based criteria alone for detecting lymph node involvement.
- Staging involves classifying the size and extent of the primary tumor and determining if the cancer has spread to lymph nodes or distant organs. Higher stages indicate larger primary tumors or spread beyond the lungs.
Graeme Mason, Planning and Corporate Affairs Director at Newcastle International Airport, gave a briefing to business leaders on April 9, 2014. He discussed how the airport is a public-private partnership and its connectivity helps drive the regional economy, supporting thousands of jobs and billions in revenue. He also covered the airport's plans to improve customer experience and facilities while supporting additional UK runway capacity and lower aviation taxes.
Michael DeCerbo is a graphic designer and illustrator based in Houston, Texas. He has a background in mixed martial arts and breakdancing which led him to tour across the US and overseas. After settling down in Texas, he has worked on a broad range of design projects for companies including promotional materials, logos, and billboards. His current role involves resetting the graphic design for over 100 formal wear store locations, which requires extensive production planning and installation. He is seeking new employment opportunities as his current department is closing in January 2013.
Jane, a 14-year-old girl, used to have a happy life until something changed within her and she felt possessed. She tries to warn her mother Judith and father Justin, but they don't believe her. Jane's behavior becomes increasingly erratic, and during an altercation with her reflection in the mirror, she transforms into a demonic creature. Judith then acknowledges something may be wrong with Jane. The story explores Jane's possession and the efforts of her family to help her.
This course have 2 parts (Design & Code).
Learning iOS dev from zero. There is many things you can do without code.
1. Define the problem you want to solve.
2. Known the basic UI component in iOS world.
3. App flow controll with navigation
4. Why we need Autolayout?
Estonian Entrepreneurial Ecosystem (the Connectors)Andrus Viirg
This document discusses the public and private connectors that support the entrepreneurial ecosystem in Estonia. It outlines the role of Enterprise Estonia, the state foundation that provides financing, advice and partnerships to support investment, trade, innovation and tourism. It also discusses accelerators, co-working spaces, grant programs, and networking organizations that help Estonian startups. Key takeaways include the importance of developing entrepreneurial mindsets through education, forming risk capital, and creating public-private partnerships to fuel serial entrepreneurship and scalable technology companies in Estonia.
This document discusses the treatment of metastatic disease in lung cancer. It emphasizes the importance of determining histology (squamous vs. non-squamous) and biomarkers to guide treatment decisions. For squamous cell carcinoma, EGFR/ALK testing is not recommended and treatment involves platinum-based doublets or cetuximab-containing regimens. For non-squamous, testing for EGFR/ALK is recommended, and if negative, initial treatment with carboplatin/pemetrexed is an option. The prognostic value of TTF-1 is also discussed, as its negativity highly predicts EGFR mutation negativity. Treatment decisions should incorporate histology, biomarker status, and other clinical factors.
Downloadable slide decks are a great tool for self study and teaching purposes. They are non-certified resources available to enhance your knowledge.
Review a downloadable slide deck by Deborah K. Armstrong, MD, covering the most clinically relevant new data reported from The Future of Antiangiogenic Therapies in Ovarian Cancer: A Series of Community and Academic Grand Rounds.
Target Audience
This activity has been designed to meet the unique learning needs of oncologists, surgeons, gynecologists, and other healthcare professionals involved in the treatment of patients with ovarian cancer.
Format: Microsoft PowerPoint (.ppt) | File size: 9.7 MB | Date posted: 8/06/2012
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of August 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
Activity Overview
Although progress continues to be made in the treatment of ovarian cancer, making clinical decisions remains a challenge due to the many treatment options available in several different settings. Selective inhibitors of the VEGF/PDGF/FGF pathways have shown activity in patients with ovarian cancer in phase II and III clinical trials either as monotherapy or in combination with other chemotherapy. Community and academic oncologists who treat patients with ovarian cancer need to stay abreast of the latest research that can affect treatment decisions and patient outcomes.
As controversy still exists regarding how and when to incorporate the use of antiangiogenic agents into the treatment paradigm for ovarian cancer patients, this case-based activity developed by expert faculty will provide clinicians with the practical application of new data into community and academic practice settings.
1) EGFR mutations are found in 10-30% of NSCLC cases and are associated with response to EGFR TKIs as first-line treatment.
2) Several studies including IPASS, EURTAC and LUX-Lung 3 have shown superior PFS for first-generation EGFR TKIs like gefitinib and erlotinib and the second-generation TKI afatinib compared to platinum-based chemotherapy as first-line treatment for EGFR mutation-positive NSCLC.
3) Meta-analyses of these studies demonstrate improved PFS for EGFR TKIs compared to chemotherapy in EGFR mutation-positive NSCLC, though OS is generally similar between the treatments
This document discusses evolving strategies for the personalized treatment of non-small cell lung cancer (NSCLC). It covers histological and molecular subtypes of NSCLC, key clinical trials of the EGFR tyrosine kinase inhibitor gefitinib, mechanisms of acquired resistance to EGFR TKIs, and approaches to managing resistance. A phase IV study showed gefitinib was effective first-line therapy for Caucasian patients with EGFR mutation-positive NSCLC, with a 69.8% response rate and favorable progression-free and overall survival. Exploratory analyses found plasma samples could accurately assess EGFR mutation status when tumor tissue was unavailable. The document reviews strategies for treating systemic and central nervous system progression after acquiring resistance to EGFR T
Treatment of Non–Small-Cell Lung Cancer with Erlotinib or Gefitinibseayat1103
This document discusses a clinical trial comparing the efficacy of erlotinib and gefitinib for the treatment of non-small cell lung cancer. The trial found that both erlotinib and gefitinib showed efficacy in NSCLC patients with EGFR mutations, with erlotinib demonstrating a median progression-free survival of 10.8 months compared to 5.4 months for standard chemotherapy in EGFR mutation-positive patients. Subsequent studies confirmed the superior efficacy of both erlotinib and gefitinib in NSCLC patients with EGFR mutations, particularly those with exon 19 deletions or L858R mutations. The document concludes by discussing the current NCCN guidelines for use of erlotinib and
New developments of targeted therapy in nsclclihua jiao
Targeted therapies have improved outcomes for patients with lung cancer harboring specific mutations. Several studies showed first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) improved response rates and progression-free survival over chemotherapy for patients with EGFR mutations. Resistance often emerges due to the T790M mutation. Irreversible EGFR TKIs like afatinib have shown activity against T790M resistance. Crizotinib demonstrated high response rates and prolonged progression-free survival in patients with anaplastic lymphoma kinase (ALK) rearrangements. New ALK inhibitors are in development. Selumetinib, a MEK inhibitor, showed clinical benefit in patients with KRAS mutations
Geoffrey Oxnard, MD, discusses the latest research in targeted therapies and molecular testing to treat lung cancer.
This presentation was originally given as part of "Living with Lung Cancer: A Forum for Patients and Caregivers" on Nov. 14, 2015 at Dana-Farber Cancer Institute in Boston, Mass.
The document summarizes clinical updates and advances in the treatment of non-small cell lung cancer (NSCLC). It discusses the incidence, subtypes and staging of NSCLC and recommendations for adjuvant therapy, targeted therapy and treatment of metastatic disease. It also reviews results from randomized trials of adjuvant chemotherapy showing improved survival compared to observation alone.
1. Receptor tyrosine kinases (RTKs) drive key cancer pathways and can be exploited as therapeutic targets, as shown by drugs like imatinib that inhibit mutated kinases in cancers.
2. RTK inhibitors have shown efficacy against cancers dependent on single kinases, but resistance often emerges through secondary mutations or bypass pathways.
3. Effective combination therapies are needed to overcome resistance, such as combining RTK inhibitors with other drugs that block downstream or bypass pathways.
- Non-small cell lung cancer is the most common malignancy worldwide and a leading cause of cancer death. It accounts for the majority (70-80%) of lung cancers.
- Imaging techniques like CT scans are important for accurately assessing the primary tumor and detecting metastasis. Positron emission tomography (PET) CT is more sensitive than size-based criteria alone for detecting lymph node involvement.
- Staging involves classifying the size and extent of the primary tumor and determining if the cancer has spread to lymph nodes or distant organs. Higher stages indicate larger primary tumors or spread beyond the lungs.
Graeme Mason, Planning and Corporate Affairs Director at Newcastle International Airport, gave a briefing to business leaders on April 9, 2014. He discussed how the airport is a public-private partnership and its connectivity helps drive the regional economy, supporting thousands of jobs and billions in revenue. He also covered the airport's plans to improve customer experience and facilities while supporting additional UK runway capacity and lower aviation taxes.
Michael DeCerbo is a graphic designer and illustrator based in Houston, Texas. He has a background in mixed martial arts and breakdancing which led him to tour across the US and overseas. After settling down in Texas, he has worked on a broad range of design projects for companies including promotional materials, logos, and billboards. His current role involves resetting the graphic design for over 100 formal wear store locations, which requires extensive production planning and installation. He is seeking new employment opportunities as his current department is closing in January 2013.
Jane, a 14-year-old girl, used to have a happy life until something changed within her and she felt possessed. She tries to warn her mother Judith and father Justin, but they don't believe her. Jane's behavior becomes increasingly erratic, and during an altercation with her reflection in the mirror, she transforms into a demonic creature. Judith then acknowledges something may be wrong with Jane. The story explores Jane's possession and the efforts of her family to help her.
This course have 2 parts (Design & Code).
Learning iOS dev from zero. There is many things you can do without code.
1. Define the problem you want to solve.
2. Known the basic UI component in iOS world.
3. App flow controll with navigation
4. Why we need Autolayout?
Estonian Entrepreneurial Ecosystem (the Connectors)Andrus Viirg
This document discusses the public and private connectors that support the entrepreneurial ecosystem in Estonia. It outlines the role of Enterprise Estonia, the state foundation that provides financing, advice and partnerships to support investment, trade, innovation and tourism. It also discusses accelerators, co-working spaces, grant programs, and networking organizations that help Estonian startups. Key takeaways include the importance of developing entrepreneurial mindsets through education, forming risk capital, and creating public-private partnerships to fuel serial entrepreneurship and scalable technology companies in Estonia.
This document discusses the treatment of metastatic disease in lung cancer. It emphasizes the importance of determining histology (squamous vs. non-squamous) and biomarkers to guide treatment decisions. For squamous cell carcinoma, EGFR/ALK testing is not recommended and treatment involves platinum-based doublets or cetuximab-containing regimens. For non-squamous, testing for EGFR/ALK is recommended, and if negative, initial treatment with carboplatin/pemetrexed is an option. The prognostic value of TTF-1 is also discussed, as its negativity highly predicts EGFR mutation negativity. Treatment decisions should incorporate histology, biomarker status, and other clinical factors.
Downloadable slide decks are a great tool for self study and teaching purposes. They are non-certified resources available to enhance your knowledge.
Review a downloadable slide deck by Deborah K. Armstrong, MD, covering the most clinically relevant new data reported from The Future of Antiangiogenic Therapies in Ovarian Cancer: A Series of Community and Academic Grand Rounds.
Target Audience
This activity has been designed to meet the unique learning needs of oncologists, surgeons, gynecologists, and other healthcare professionals involved in the treatment of patients with ovarian cancer.
Format: Microsoft PowerPoint (.ppt) | File size: 9.7 MB | Date posted: 8/06/2012
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of August 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
Activity Overview
Although progress continues to be made in the treatment of ovarian cancer, making clinical decisions remains a challenge due to the many treatment options available in several different settings. Selective inhibitors of the VEGF/PDGF/FGF pathways have shown activity in patients with ovarian cancer in phase II and III clinical trials either as monotherapy or in combination with other chemotherapy. Community and academic oncologists who treat patients with ovarian cancer need to stay abreast of the latest research that can affect treatment decisions and patient outcomes.
As controversy still exists regarding how and when to incorporate the use of antiangiogenic agents into the treatment paradigm for ovarian cancer patients, this case-based activity developed by expert faculty will provide clinicians with the practical application of new data into community and academic practice settings.
1) The POPE study was a randomized, double-blind trial that assessed whether the NSAID diclofenac was effective in reducing post-operative pericardial effusion volume compared to placebo.
2) 196 patients with moderate to large pericardial effusions more than 7 days after cardiac surgery were randomized to receive either diclofenac or placebo for 14 days.
3) The primary outcome of mean pericardial effusion grade decrease from baseline to end of treatment showed no significant difference between the diclofenac and placebo groups. Secondary outcomes including late tamponade rates were also similar between groups.
4) The study concluded that NSA
Jeremy Chapman - Australia - Tuesday 29 - Hematopoietic Stem Cellsincucai_isodp
This document summarizes research on hematopoietic stem cell transplantation. It finds that only a small percentage of minority patients receive bone marrow transplants due to a lack of compatible donors. Outcomes depend on disease stage and HLA matching, with lower risk disease having better outcomes with a single HLA mismatch. Cord blood transplants show promise as an alternative to bone marrow, especially for children, though cell dose and HLA matching impact outcomes. Larger studies are needed to better understand long-term effects.
Disease modifying treatments for multiple sclerosis have evolved significantly over time. Early treatments focused on interferon-beta, which showed moderate effectiveness in reducing relapses and disability progression. Newer monoclonal antibody treatments such as natalizumab provided greater reductions in disease activity but also carried increased safety risks. The latest oral therapies including fingolimod, teriflunomide, dimethyl fumarate, and laquinimod provide over 50% reductions in relapse rates compared to earlier treatments with generally improved safety profiles. Ongoing research continues to evaluate new mechanisms of action to more effectively treat multiple sclerosis.
Costo efficacia della terapia con sorafenib nel trattamento dell’HCC - Gastro...Gastrolearning
Gastrolearning III lezione
Costo efficacia della terapia con sorafenib nel trattamento dell’HCC - Prof. C. Cammà (Università di Palermo)
www.gastrolearning.it
In 2011, the treatment armamentarium dramatically expanded with the approval of the anti-CTLA4 antibody ipilimumab and the BRAF inhibitor vemurafenib. Oncology nurses who care for patients with melanoma are beginning to administer these new agents and have numerous questions regarding their efficacy, different response patterns, unique toxicity profiles, how they may be integrated into current treatment regimens, and how to educate patients on their benefits and risks.
Downloadable slide decks are a great tool for self study and teaching purposes. They are non-certified resources available to enhance your knowledge.
Review a downloadable slide deck by Peg Esper, MSN, MSA, RN, APN-BC, AOCN®, covering the most clinically relevant new data reported from Metastatic Melanoma: An Oncology Nurse Workshop on Novel Treatments, Adverse Event Management, and Patient Education.
Target Audience
This activity has been designed to meet the educational needs of oncology nurses involved in the treatment of patients with advanced melanoma.
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of May 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CE provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
For more information:
http://imeronline.com/gxpsites/hgxpp001.aspx?11,52,304,O,E,0,,744;561;8362
Susan O'Brien, M.D., Professor, Dept. of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center: Newest Strategies in the Treatment of CML/CLL presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center.
1) The study examined outcomes in patients with heart failure who were at high risk, finding that at 6 months their risk was approximately 3.8 times higher.
2) Baseline characteristics were similar between the eplerenone and placebo groups, including average age of 64, 72% males, mean ejection fraction of 33%, and 32% with diabetes.
3) For the primary endpoints of total mortality and cardiovascular mortality or hospitalization, eplerenone demonstrated a 15% and 13% reduced risk respectively compared to placebo.
1) A clinical trial assessed whether chelation therapy improved quality of life outcomes in patients with stable coronary artery disease and a history of heart attack.
2) The trial found no consistent or sustained improvements in domains of health-related quality of life, including physical and mental functioning, with chelation therapy over 2 years of follow up.
3) A subgroup analysis found a potential benefit of chelation therapy for patients with angina symptoms at baseline, but no benefit was seen for patients with heart failure symptoms.
Atrial fibrillation (AF) is the most frequently diagnosed cardiac rhythm disorder. It affecting 2.5 million people in the United States, and may be associated with an increased risk for death, congestive heart failure, and stroke. Our cardiac electrophysiologist will review the latest treatment options for patients with AF, including recent advances in pharmacologic therapy to keep patients heart rhythms normal. He also will discuss catheter ablation to eliminate sources of AF and anticoagulation to prevent thromboembolic strokes. Presented by Summit Medical Group cardiologist, Roy Sauberman, MD, FACC
Andre Goy, MD, Chairman and Chief of Lymphoma, John Theurer Cancer Center at Hackensack University Medical Center - Treatment of Large Cell Lymphoma
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
This document summarizes research on two proteins - Human Retinol Binding Protein-4 (RBP4) and Kvβ2, a subunit of the Kv1 potassium channel. For RBP4, the researcher optimized PCR conditions to amplify the gene and assessed RBP4's proposed role in insulin resistance and diabetes. For Kvβ2, the researcher overexpressed and purified the protein, then tested the inhibitory effects of rutin, quercetin, and resveratrol on Kvβ2 activity. The results provide new insights into physiological processes involving the Shaker potassium channel and identify resveratrol as a potential inhibitor of Kvβ2 activity. Overall, the research yielded beneficial PCR guidelines
Patti G. Vecchi e nuovi anticoagulanti orali a confronto. ASMaD 2013Gianfranco Tammaro
This document summarizes the results of several clinical trials comparing new oral anticoagulants to warfarin for preventing stroke in atrial fibrillation patients. The RELY trial found that dabigatran 150mg reduced stroke risk compared to warfarin, with similar major bleeding rates. Rivaroxaban in ROCKET-AF reduced stroke risk similarly to warfarin with similar bleeding rates. Apixaban in ARISTOTLE reduced stroke and major bleeding compared to warfarin. Overall, the new oral anticoagulants were found to be non-inferior or superior to warfarin for stroke prevention with similar or better safety profiles.
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
1) A phase 3 trial of abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive metastatic castration-resistant prostate cancer patients showed improved radiographic progression-free and overall survival for the abiraterone arm.
2) At the first interim analysis when 425 overall survival events occurred, the hazard ratio for overall survival was 0.66 with a p-value of 0.0034, crossing the pre-specified boundary for statistical significance.
3) Secondary endpoints including time to opiate use, chemotherapy initiation, performance status deterioration, and prostate specific antigen progression were also all significantly prolonged in the abiraterone arm.
This document outlines an NSCLC treatment algorithm based on stage and molecular profiling results. It recommends surgical resection for early stage disease when possible. For later stages, it suggests chemotherapy, immunotherapy, targeted therapy, or combinations based on mutation status and PD-L1 levels. Newer targeted therapies and antibody-drug conjugates are highlighted for specific mutations like EGFR, ALK, ROS1, RET, MET, KRAS G12C, and HER2.
Chair and Presenter, Jonathan D. Spicer, MD, PhD, FRCSC, Sara Najmeh, MD, and Paula A. Ugalde Figueroa, MD, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC activity titled “Neoadjuvant, Adjuvant, or Both: How to Solve the Puzzle of Perioperative Immunotherapy, Individualize Treatment Plans, and Improve Cure Rates in Resectable NSCLC.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3K8tKH9. CME/MOC credit will be available until June 5, 2024.
Chair, Stephen V. Liu, MD, Melissa L. Johnson, MD, Benjamin Levy, MD, and Prof. Solange Peters, MD, PhD, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC/AAPA activity titled “Amplifying the ADC Advantage: How to Fulfill the Potential of Antibody–Drug Conjugates as the Next Frontier in Precision Lung Cancer Care.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/3kv9A15. CME/MOC/AAPA credit will be available until July 3, 2024.
Similar to West xcenda molec testing sf oct 2011 revised final (20)
Moving Beyond the Hype: 3 Key Steps for Personalized Cancer MedicineH. Jack West
The concept of personalized or precision medicine is hot enough that President Obama is launching initiatives for it, but how close is it to moving beyond hype?
Here are 3 key steps we need to attain to know that personalized medicine, particularly in the world of cancer care, isn't just delivering false hope for most patients.
This document summarizes the top five highlights in lung cancer in 2014. They are:
1) CMS approved low-dose CT screening for high-risk patients, which could improve early detection and survival rates for lung cancer.
2) New targeted therapies were approved that can overcome resistance for EGFR and ALK-positive NSCLC, including ceritinib for ALK resistance and AZD9291 and rociletinib for EGFR T790M mutation resistance.
3) New treatments provided small survival benefits of around 1.5-2 months for broad populations of previously treated advanced NSCLC, including Cyramza and nintedinib.
4) Immune checkpoint inhibitors like PD-1
Best of ASCO Metastatic Non-Small Cell Lung CancerH. Jack West
Dr. Jack West's presentation on highlights in advanced non-small cell lung cancer from ASCO 2014, focusing on new agents ramucirumab and necitumumab for broad NSCLC populations, crizotinib and ceritinib for ALK-positive NSCLC, EGFR inhibitor-options of afatinib and bevacizumab added to erlotinib for first line treatment of EGFR mutation-positive NSCLC, and AZD9291 or CO1686 for EGFR mutation-positive patients with acquired resistance.
10 Key ASCO 2014 Presentations in Lung CancerH. Jack West
Dr. Jack West offers a list of 10 of the most important, timely abstract presentations in lung cancer, both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), at the annual ASCO 2014 conference.
Transitioning Survival from Months to Years in Advanced Non-Small Cell Lung C...H. Jack West
Dr. Jack West reviews the evolution of new treatment options for advanced NSCLC that have steadily improved survival. This progress has been incremental but now means that an ever-growing proportion of patients with advanced NSCLC have a realistic promise of potentially living several years after their diagnosis and the start of treatment. Note that this presentation does not address advances in immunotherapy, which were covered in a separate talk at the same conference at which Dr. West delivered this presentation.
What is the value of maintenance therapy in advanced NSCLC, and who should ge...H. Jack West
Dr. Jack West reviews the rationale for maintenance therapy in advanced NSCLC, what the evidence shows about its value, the limitations, and thoughts on which patients should or should not pursue it.
50 Shades of Cancer Progression: The Continuum of Progression & How We Decide...H. Jack West
Dr. Jack West reviews the importance of assessing the degree of progression when interpreting whether to change treatment of a cancer. It is important to ask not only whether a cancer has progressed, but HOW it has done so, and how much?
Key Clinical Implications of how a Cancer EvolvesH. Jack West
Cancer adapts and evolves over time and under the selective pressure of systemic treatment, becoming increasingly resistant over time. This brief slidedoc fo summarizes key points in how cancer adaptation leads to resistance and changes our treatment recommendations.
Treating Invisible Disease: How the Probability of Disease We Can't See Chang...H. Jack West
A brief slidedoc that reviews why we focus on both the cancer we can see and the potential cancer we can't when we shape our treatment recommendations in lung cancer and many other cancers.
Changes Afoot: Changing Relationships between Engaged Patients and Docs in Ca...H. Jack West
Discussion of how online patient communities and social media are changing relationships between engaged patients and oncologists, improving quality of cancer care.
Patient and doc engagement online westH. Jack West
The document discusses how the relationship between doctors and patients is changing from a unidirectional model to a bidirectional model due to the increasing amount of medical information available online. It notes that the rate of new medical information has more than doubled in the last 20 years, making it impossible for doctors to know everything. As a result, patients are increasingly informed and motivated to help themselves by seeking information from social networks and online resources. This is shifting the interaction between doctors and patients to a more collaborative bidirectional model where physicians are no longer expected to have all the answers and patients play a more active role in their own care.
West Immunotherapy, Vaccines for Lung Cancer Mage-A3, Stimuvax, and LucanixH. Jack West
This document summarizes information about three cancer vaccines - MAGE-A3, Stimuvax (L-BLP25, Tecemotide), and Lucanix (Belagenpumatucel-L). It discusses past and ongoing clinical trials of these vaccines in non-small cell lung cancer (NSCLC), including trial designs, results, and potential efficacy in patient subgroups. Key information presented includes Phase 3 trial results for Stimuvax showing a possible survival benefit in patients receiving concurrent chemotherapy and radiation, and evidence that Belagenpumatucel-L may benefit certain NSCLC patient subgroups based on retrospective analyses.
Acquired Resistance to Targeted Therapy in EGFR and ALK-Positive Lung Cancer:...H. Jack West
This is a presentation I did for a meeting on new general management of acquired resistance in 2014, including the concept of local therapy for limited progression, and new treatment approaches and new agents for this setting. It features discussion of several of the most important trials.
West asco clin mgmt acquired resistance tk isH. Jack West
1) Acquired resistance to targeted therapies like EGFR TKIs in NSCLC can present with heterogeneous clinical patterns from isolated progression to more diffuse progression due to diverse molecular mechanisms.
2) Not all detectable progression requires an immediate treatment change, as some may not represent clinically significant progression. Continuing targeted therapy beyond progression may be reasonable in some cases.
3) For isolated or "oligoprogressive" acquired resistance, local therapy combined with continued targeted therapy is an option. Diffuse progression may warrant switching to chemotherapy, with the potential to later rechallenge with targeted therapy.
4) Prospective randomized trials are needed to define optimal treatment approaches for acquired resistance, and trials of novel agents could help special populations.
West egfr mutation acquired resistanceH. Jack West
Review by Dr. H. Jack West of current understanding of mechanisms behind and emerging treatment options for patients with advanced NSCLC with acquired resistance to EGFR tyrosine kinase inhibitors after a good initial response.
Dr. Jack West Oncology 2.0, to WA AG's OfficeH. Jack West
Dr. H. Jack West, medical oncologist and Founder/CEO of Global Resource for Advancing Cancer Education (GRACE, www.CancerGRACE.org), spoke to WA state Attorney General's office about the changing landscape of cancer care and how the internet and specifically online patient communities and education will become disruptive in changing the patient/physician dynamic.
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
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.
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
10 Benefits an EPCR Software should Bring to EMS Organizations Traumasoft LLC
The benefits of an ePCR solution should extend to the whole EMS organization, not just certain groups of people or certain departments. It should provide more than just a form for entering and a database for storing information. It should also include a workflow of how information is communicated, used and stored across the entire organization.
The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
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.
Kosmoderma Academy, a leading institution in the field of dermatology and aesthetics, offers comprehensive courses in cosmetology and trichology. Our specialized courses on PRP (Hair), DR+Growth Factor, GFC, and Qr678 are designed to equip practitioners with advanced skills and knowledge to excel in hair restoration and growth treatments.
West xcenda molec testing sf oct 2011 revised final
1. Molecular Markers and Testing Strategies
in Advanced Non-Small Cell Lung Cancer
Howard (Jack) West, MD
Swedish Cancer Institute
Seattle, WA
Challenging Cases
in Breast & Lung Cancer
San Francisco, CA
October 22, 2011
2. Why do molecular testing?
• To improve clinical outcomes
– Give best treatment first (timing of EGFR TKI Rx)
– To provide access to agent (crizotinib for ALK-
positive)
– To identify subsets who might benefit from targeted
therapy (cetuximab?)
• To facilitate clinical research
– May improve patient outcomes
– Better understanding of molecular oncology
3. IPASS: Gefitinib vs. Carbo/Paclitaxel as
First Line Rx in Asian Never- or Light Ex-Smokers
R Carbo/Paclitaxel IV
Advanced NSCLC
No Prior Systemic Therapy A every 3 weeks
Never-/Light Former Smoker N
N = 1217 Gefitinib 250 mg/day
D
• Primary Endpoint: Progr-Free Survival (PFS)
• Biomarker analysis
Mok, NEJM 2009
4. IPASS: Objective Response Rate by
EGFR Mutation Status
Gefitinib
71.2% Carboplatin / paclitaxel
EGFR M+ odds ratio (95% CI) = 2.75
(1.65, 4.60), p=0.0001
Overall 47.3% EGFR M- odds ratio (95% CI) = 0.04
response (0.01, 0.27), p=0.0013
rate (%)
23.5%
1.1%
(n=132) (n=129) (n=91) (n=85)
Odds ratio >1 implies greater chance of response on gefitinib
Mok, NEJM 2009
5. IPASS Study: OS
Overall Population
Probability of Survival
1.0
HR: 0.90 (95% CI: 0.79-1.02; P = .109)
0.8
Gefitinib (n = 609)
0.6 Carboplatin/paclitaxel (n = 608)
0.4
0.2
0
0 4 8 12 16 20 24 28 32 36 40 44 48 52
Time Since Random Assignment (Mos)
EGFR Mutation Positive EGFR Mutation Negative
Probability of Survival
Probability of Survival
1.0 HR: 1.00 (95% CI: 0.76-1.33; P = .990) 1.0 HR: 1.18 (95% CI: 0.86-1.63; P = .309)
0.8 Gefitinib (n = 132) 0.8 Gefitinib (n = 91)
Carboplatin/paclitaxel (n = 129) Carboplatin/paclitaxel (n = 85)
0.6 0.6
0.4 0.4
0.2 0.2
0 0
0 4 8 12 16 20 24 28 32 36 40 44 48 52 0 4 8 12 16 20 24 28 32 36 40 44 48 52
Time Since Random Assignment (Mos) Time Since Random Assignment (Mos)
Fukuoka M, et al. J Clin Oncol. 2011;29:2866-2874.
6. IPASS Study: PFS by EGFR Status
• EGFR mutation status most predictive, EGFR gene
amplification also significantly predictive, but less
Fukuoka M, et al. J Clin Oncol. 2011;29:2866-2874.
7. Prevalence of EGFR Mutations
Phenotype of NSCLC Patient Prevalence of EGFR Mutation
All 10% to15%
Caucasian never-smokers ~35%
Asian never-smokers ~65%
Jackman DM et al. ASCO 2008 Annual Meeting. Abstract 8035.
8. MSKCC Continuum of Tobacco Exposure
and EGFR Mutations
• Looking for exon 19 or 21 mutations in tumors from 265 pts
with detailed smoking history
Pham, JCO 2006
9. Prevalence of EGFR Mutations by Smoking
Status: Lung AdenoCa at MSKCC
• Testing for exon 19 or 21 mutation in 2142 adenocarcinomas at
MSKCC
• Rate: EGFR mut’ns seen in 52% of never-smokers, 15% of former
smokers, and 6% of current smokers
D’Angelo, J Clin Oncol 2011
10. Prospective Trials of EGFR TKIs vs. Chemo
in EGFR Mutation (Exons 19, 21) Population
RR PFS (mo) OS (mo)
Trial N Rx
TKI Chemo TKI Chemo TKI Chemo
Maemondo Gefitinib vs.
230 74% 31% 10.8 5.4 30.5 23.6
NEJ002 Carbo/Pac
Mistudomi Gefitinib vs.
172 62% 32% 9.2 6.3 30.9 N.R.
WJTOG3405 Cis/Doce
Zhao Erlotinib vs.
165 83% 36% 13.1 4.6 N.R. N.R.
OPTIMAL Carbo/Gem
Rosell Erlotinib vs.
174 58% 15% 9.4 5.2 N.R. N.R.
EURTAC Plat Doublet
Maemondo, NEJM 2010; Mistudomi, Lancet Oncol 2010;
OPTIMAL, Lancet Oncol 2011; Rosell, ASCO 2011
11. TORCH Study:
Chemo Erlotinib vs. Erlotinib Chemo
Gridelli, ASCO 2010, #7508 Standard arm
R Cis/Gemcitabine Erlotinib 150 mg/d
Advanced NSCLC
No clinical or A x 6 cycles
molecular selection N Experimental arm
N = 760, Cis/Gemcitabine
closed by DSMB D Erlotinib 150 mg/d x 6 cycles
Order of therapy matters: get best treatment in at first opportunity
12. TORCH Study: Efficacy Analysis
Efficacy Outcome Erlotinib → Chemo → HR P
Chemo Erlotinib (95% CI) Value
(n = 380) (n = 380)
1.40
Median OS, mos 7.7 10.9 .002
(1.13-1.73)
Median PFS,* mos 2.2 5.7 Not reported
Objective response,† % 18 32
With first-line treatment
• CR <1 1
• PR 9 27 Not reported
With second-line treatment
• CR 1 <1
• PR 9 6
*Assessment of first-line treatment only.
†Intent-to-treat population.
Gridelli C, et al. ASCO 2010. Abstract 7508.
13. KRAS Mutations and Resistance
to EGFR Inhibitors
RR OS
Trial N Agent
Wild Type Mutant Wild Type Mutant
INTEREST 275 Gefitinib 10% 0% 7.5 mos 7.8 mos
Gefitinib or
Jackman 116 5% 0% 11.8 mos 13 mos
erlotinib
Gefitinib or
Massarelli 70 10% 0% 9.4 mos 5 mos
erlotinib
Shepherd 206 Erlotinib 10.2% 5% 7.5 mos 3.7 mos
Miller* 101 Erlotinib 32% 0% 21 mos 13 mos
*Patients with BAC.
Douillard. ASCO. 2008 (abstr 8001); Jackman. ASCO. 2008 (abstr 8035);
Massarelli. Clin Cancer Res. 2007;13:2890; Shepherd. ASCO. 2007 (abstr 7571);
Miller. J Clin Oncol. 2008;26:1472.
14. Waterfall Plot of Response on Erlotinib in
Advanced BAC, with Molecular Correlates
• Most but not all of the best responders carry EGFR mutations
• Many with minor response and even some with PR have neither EGFR
mutation nor EGFR gene amplification
• Several KRAS mutation patients have stable disease or even minor responses
(which very likely correlate with modest clinical benefit)
• Selecting on basis of EGFR mutations or FISH positivity would filter out many
beneficiaries; selecting by KRAS would also eliminate many w/SD or MR
Miller, JCO 2008
15. INTEREST Trial: A Wide Range of Very
Unhelpful Molecular Markers
Worldwide trial, second line docetaxel vs. gefitinib, N = 1466
OS DFS
Douillard, JCO 2010
16. EML4-ALK Translocations in NSCLC
Soda et al., Nature 448: 561-566, 2007
EML4-ALK frequency:
~4% (64/1709)
Primarily adenoCa, minimal
or no smoking history
Bang, ASCO 2010
#2 (Plenary), then
NEJM
17. 48 yo Female Never Smoker with Stage IV NSCLC
Positive for EML4-ALK
Pre-Treatment After 2 cycles PF-02341066
18. 77% of Patients with ALK-positive NSCLC
Remain on Crizotinib Treatment
• Duration of treatment
(median: 5.7 months)
0–3 mo 13 pts
>3–6 mo 29 pts
Individual patients
>6–9 mo 24 pts
>9–12 mo 9 pts
>12–18 mo 4 pts
>18 mo 3 pts
• Reasons for discontinuation
– Related AEs 1
– Non-related AEs 1
– Unrelated death 2
– Other 2
– Progression 13
0 3 6 9 12 15 18 21
Treatment duration (months)
N=82; red bars represent discontinued patients
19. The Majority of ALK-Positive Patients are
Never-Smokers
Never smoker
Light smoker
Smoker
ALK-Positive
Shaw et al. ASCO 2010
20. Mutation Status By Smoking History
Caucasians
18% 2%
ALK
EGFR
WT/WT
≤10 pack-years >10 pack-years
(N=255) (N=232)
Shaw et al. ASCO 2010
21. Mutation Status By Smoking History
Asians
8%
EGFR
KRAS
ALK
WT/WT/WT
1.2%
Never-smokers Ever-smokers
(N=127) (N=82)
Wong et al., Cancer 2009;115:1723-33.
22. Mutation Status in
Asian Never-Smokers
N=52
Sun et al. JCO 2010;28:4616-20
23. FLEX: Study Design
Adv NSCLC R Cis d1/Vin d1,8
EGFR IHC 1 +
No prior Rx
A
No brain mets N Cis d1/Vin d1,8
(N = 1,125) D + weekly cetuximab
• Stratification • Primary end point: OS
• – ECOG PS: 0/1 vs. 2
• – Stage: IIIB (wet) vs. IV • Secondary end points: PFS, RR, QOL, safety
Pirker et al, Lancet 2010
24. ITT (n=1125) Median OS 1-year survival
▬ CT + cetuximab 11.3 mo 47%
(n=557)
▬ CT 10.1 mo 42%
Overall survival (%)
(n=568)
HR=0.871 [95% CI 0.762–0.996]; p=0.044
Months
Pirker, Lancet 2010
25. EGFR Expression in FLEX Study
O‘Byrne,
Lancet Oncol 2011
Low EGFR Expression High EGFR Expression
Parameter
CT CT + Cetuximab CT CT + Cetuximab
Median OS
10.3 9.8 9.6 12.0
(months)
26. FLEX High EGFR IHC, by Histology
Adenocarcinoma (N = 135) Squamous (N = 144)
27. NCCN Guidelines (October, 2011)
• Patients with non-squamous advanced
NSCLC should be tested for EGFR mutation
and ALK rearrangement
• Treatment in this setting should be guided by
results of this testing
Caveat:
NCCN expertise: cancer treatment, independent of cost
NCCN non-expertise: health care economics/value of Rx
28. ASCO Guidelines (Sept, 2011) Re:
EGFR inhibitors
• Most patients should not receive EGFR TKI
as part of 1st line treatment
• For those with EGFR mut’n, EGFR TKI alone
may be recommended
• For patients receiving cis/vinorelbine,
cetuximab may be added
29. ASCO Guidelines (Sept, 2011) Re:
Molecular Testing
• ASCO recognizes that most patients with NSCLC may not
have any special molecular tests…these molecular tests
remain investigational, and selecting treatment based on
molecular tests has not been shown to improve a patients’s
overall length of live.
• Therefore, ASCO does not recommend using any routine
molecular analysis of tumor tissue to guide treatment
decisions at this time. For patients with an EGFR mutation,
erlotinib or gefitinib may be the best first-line therapy, but
may also work well as a second or third-line treatment.
• Larger tissue samples recommended when performing Bx,
to facilitate future research and maximize eligibility in trials.
30. My Conclusions:
Clinical Management Decisions
• EGFR TKIs
– EGFR TKI shouldn’t be 1st line Rx in unselected pts.
– If you know EGFR mut’n +, I’d give earlier >> later
– Importantly, EGFR wild type doesn’t mean no benefit
from EGFR TKI in maintenance or later
• ALK positivity is KEY to access to crizotinib
major benefit
• EGFR IHC possibly very helpful in selecting for
cetuximab
31. Setting the Balance:
Where Do You Fit on the Spectrum?
Test enriched Test everyone to
population miss NOBODY
$5K/pos test
Never-smoker, adeno
Test 12%, find 40%
Adeno (any smoking Hx)
Test 45%, find 90%
Adeno (any) + non-squam light smokers,
Test 67%, find 95%
All non-squamous adv NSCLC
Test 75%, find 97%
All advanced NSCLC
Test 100%, find 100%
$60K/pos test
(All numbers approximate)
32. My Conclusions: Who To Test?
• Selective vs. everything for everyone?
– I favor a selective approach based on histology &
smoking status, not (yet) testing for all patients
• Remember fallibility of histology assignment
– EGFR mut’n pts can still get comparable benefit as
maintenance or 2nd line
– Stronger argument for ALK testing (pos = access)
– This is a clinical judgment, with ASCO and NCCN
endorsing different conclusions
– The only wrong answer is a dogmatic one