Www.asco.org/pco/egfrwww.asco.org/pco/egfr ©American Society of Clinical Oncology 2011. All rights reserved - American Society of Clinical Oncology Provisional.

Slides:



Advertisements
Similar presentations
IRESSA A Case Study in Personalised Medicine Dr Rose McCormack
Advertisements

Stage IV NSCLC slide set.
James R. Rigas Comprehensive Thoracic Oncology Program
Zeroing in on Non-Small Cell Lung Cancer: Integrating Targeted Therapies into Practice.
Treatment in Advanced Non-Small Cell Lung Cancer.
Biomarker Analyses in CLEOPATRA: A Phase III, Placebo-Controlled Study of Pertuzumab in HER2- Positive, First-Line Metastatic Breast Cancer (MBC) Baselga.
Questions and answers about PARAMOUNT: phase III study of pemetrexed continuation maintenance therapy in advanced non-squamous NSCLC.
American Society of Clinical Oncology Endorsement of the Cancer Care Ontario (CCO) Practice Guideline on Adjuvant Ovarian Ablation (OA) in the Treatment.
1 Sitemap Storyflow Title slideOverview slide13.6 months PFSSymptom controlQoL OS across 7 trials3 months OS > 12 month OS Summary slide.
Using Non-targeted Therapies in Targeted Lung Cancer Populations Nathan Pennell, M.D., Ph.D. September 6, 2014.
A Phase III Randomized, Double-Blind, Placebo-Controlled Trial of the Epidermal Growth Factor Receptor Inhibitor Gefitinb in Completely Resected Stage.
Cost of & Access to Molecularly Targeted Therapies as Barriers to Optimal Care H. Jack West, MD Swedish Cancer Institute Seattle, WA Global Resource for.
Tumour growth is angiogenesis dependent Judah Folkman 1971 VEGF gene identified and EGFR isolated 1980s Meta-analyses confirm survival benefit with chemotherapy.
Randomized Phase II Trial of Erlotinib (E) Alone or in Combination with Carboplatin/Paclitaxel (CP) in Never or Light Former Smokers with Advanced Lung.
EGFR Mutation Testing From the Pathologist’s Point of View
Randomized Phase II trial of erlotinib (E) alone or in combination with carboplatin/paclitaxel (CP) in never or light former smokers with advanced lung.
Non-Small Cell Lung Cancer Genetic Predictors Sacha Rothschild, MD PhD Medical Oncology.
Detection of Mutations in EGFR in Circulating Lung-Cancer Cells Colin Reisterer and Nick Swenson S. Maheswaran et al. The New England Journal of Medicine.
CRC-1 The Need for 3rd-Line Therapy in Non-Small Cell Lung Cancer Frances A. Shepherd, MD Scott Taylor Chair in Lung Cancer Research Princess Margaret.
CR-1 Concluding Remarks and Risk/Benefit Summary Mace L. Rothenberg, MD Professor of Medicine Vanderbilt Ingram Cancer Center.
Network Experience of TKI inhibitors as 1 st line use in advanced NSCLC Dr Jill Gardiner and Mr Steve Williamson April 2012.
First-Line TKI Use in EGFR Mutation-Positive NSCLC
Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI) in Non-Small Cell Lung Cancer (NSCLC) Victor.
EGFR Mutation: Clinical Evidence and Resistance to TKIs
Please note, these are the actual video-recorded proceedings from the live CME event and may include the use of trade names and other raw, unedited content.
IRESSA: A journey of experience from broad to biomarker populations
Lung cancer perspectives. Targeted therapy : one for all or a few for one ? Miklos Pless, Winterthur
Result of Interim Analysis of Overall Survival in the GCIG ICON7 Phase III Randomized Trial of Bevacizumab in Women with Newly Diagnosed Ovarian Cancer.
HER2 POSITIVE BREAST CARCINOMA IN THE PRE AND POST ADJUVANT ANTI-HER-2 THERAPY ERA: A SINGLE ACADEMIC INSTITUTION EXPERIENCE IN THE SETTING OUTSIDE OF.
1Bachelot T et al. Proc SABCS 2010;Abstract S1-6.
CheckMate 025: A randomized, open-label, phase III study of nivolumab versus everolimus in advanced renal cell carcinoma Padmanee Sharma, Bernard Escudier,
Treatment Regimens of HER2+ Adjuvant Patients (Actuals) Source: Genentech ASCO 2005 (data release) Nov 2006 (Approval)
Please note, these are the actual video-recorded proceedings from the live CME event and may include the use of trade names and other raw, unedited content.
© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey Lung Cancer and Gefitinib  Lung cancer statistics in the.
CR-1 Actions Ongoing Clinical Development Judith S. Ochs, MD.
©American Society of Clinical Oncology All rights reserved. Extended RAS Gene Mutation Testing in Metastatic.
Professor Martin Schuler MD West German Cancer Center Essen, Germany
Treatment of advanced NSCLC:
Final Efficacy Results from OAM4558g, a Randomized Phase II Study Evaluating MetMAb or Placebo in Combination with Erlotinib in Advanced NSCLC Spigel DR.
Overall survival in NSCLC
Kang Y et al. Proc ASCO 2010;Abstract LBA4007.
until tumour progression until tumour progression
Sumitra Thongprasert, MD
A Discussion on Biologic Agents in Gastric Cancer Treatment Yoon-Koo Kang, MD Professor of Medicine Asan Medical Center University of Ulsan College of.
Clinicopathologic Features of EML4-ALK Mutant Lung Cancer Shaw AT et al. ASCO 2009; Abstract (Poster)
Biomarker analyses from a phase III, randomized, open-label, first-line study of gefitinib (G) versus carboplatin/paclitaxel (C/P)
Personalized medicine in lung cancer R4 김승민. Personalized Medicine in Lung Cancer patients with specific types and stages of cancer should be treated.
First line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer – a Cochrane Collaboration.
Mok TS, Wu SL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361: Gefitinib Superior.
Adjuvant and Neoadjuvant Therapy in Non- Small Cell Lung Cancer Seminars in Oncology 2oo5;32 (suppl 2):S9-S15 Kyung Hee Medical Center Department of Thoracic.
Weekly Paclitaxel Combined with Monthly Carboplatin versus Single-Agent Therapy in Patients Age 70 to 89: IFCT-0501 Randomized Phase III Study in Advanced.
Samsung Genome Institute Samsung Medical Center
Belani CP et al. ASCO 2009; Abstract CRA8000. (Oral Presentation)
Rosell R et al. Proc ASCO 2011;Abstract 7503.
Treatment With Continuous, Hyperfractionated, Accelerated Radiotherapy (CHART) For Non-Small Cell Lung Cancer (NSCLC): The Weston Park Hospital Experience.
Comparison of Clinical Outcomes Following Gefitinib and Erlotinib Treatment in Non– Small-Cell Lung Cancer Patients Harboring an Epidermal Growth Factor.
Patient Case 1 Patient Case 1: PET/CT Scan.
Regulatory Industry Statistics Workshop 2018
Meta-analysis of randomised phase III clinical trials comparing EGFR tyrosine kinase inhibitor (TKI) shows that male patients with non-small cell lung.
EGFR Inhibitors in Advanced NSCLC: Who, When, and Why?
FDA Reviews Approval for Iressa™
Chapter 3 Treatment guidelines for NSCLC that does not have targetable driver mutations.
Meta-analysis of randomised phase III clinical trials with ALK inhibitors in non-small cell lung cancer (NSCLC) showing similar benefit in male patients.
Detection rate for EGFR mutations in cfDNA.
Meta-Analysis of First-Line Therapies in Advanced Non–Small-Cell Lung Cancer Harboring EGFR-Activating Mutations  Benjamin Haaland, PhD, Pui San Tan,
Clinical courses of patients.
Comparison of Clinical Outcomes Following Gefitinib and Erlotinib Treatment in Non– Small-Cell Lung Cancer Patients Harboring an Epidermal Growth Factor.
Kaplan–Meier curve for progression-free survival for gefitinib versus doublet chemotherapy in three phase III trials in first-line nonsmall cell lung cancer.
Kaplan–Meier analysis of PFS and OS in patients with advanced non-small cell lung cancer with adenocarcinoma histology with time since start of first-line.
Patterns of clinical relapse and algorithm for the therapeutic strategy when AR to EGFR TKI occurs in patients with EGFR-mutant NSCLC. *After discussion.
Presentation transcript:

©American Society of Clinical Oncology All rights reserved - American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non- Small Cell Lung Cancer Considering First-Line EGFR Tyrosine-Kinase Inhibitor Therapy

©American Society of Clinical Oncology All rights reserved - The Provisional Clinical Opinion “Based on the results of five phase III RCTs, patients with advanced non-small cell lung cancer of the lung who are being considered for first-line therapy with an EGFR TKI (patients who have not previously received chemotherapy or an EGFR TKI) should have their tumor tested for EGFR mutations to determine which is an appropriate first-line therapy: an EGFR TKI or chemotherapy.”

©American Society of Clinical Oncology All rights reserved - INTRODUCTION The American Society of Clinical Oncology (ASCO) has established a rigorous, evidence-based approach—the provisional clinical opinion (PCO)— to offer a rapid response to emerging data in clinical oncology The PCO is intended to offer timely clinical direction to ASCO members following publication or presentation of potentially practice-changing data from major studies

©American Society of Clinical Oncology All rights reserved - INTRODUCTION This PCO addresses the clinical utility of epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non-small cell lung cancer (NSCLC) to predict response to first-line therapy with EGFR tyrosine kinase inhibitors (TKIs; erlotinib or gefitinib)

©American Society of Clinical Oncology All rights reserved - Statement of the Clinical Issue In the United States, approximately 15% of patients with adenocarcinoma of the lung harbor activating EGFR mutations. The majority of these mutations are in exons 19 and 21 of the EGFR gene

©American Society of Clinical Oncology All rights reserved - Statement of the Clinical Issue Phase III randomized controlled trials (RCTs) of EGFR tyrosine kinase inhibitors in the first- line setting have shown a benefit in response and progression-free survival (PFS), but not overall survival (OS), for patients with EGFR- mutated NSCLC who received an EGFR TKI in first-line treatment

©American Society of Clinical Oncology All rights reserved - Statement of the Clinical Issue Greater than 90% of patients included in the majority of these trials had adenocarcinoma of the lung. Currently, neither erlotinib nor gefitinib has been approved for first-line therapy of lung cancer by the US Food and Drug Administration (FDA)

©American Society of Clinical Oncology All rights reserved - Literature Review and Analysis This PCO addresses using epidermal EGFR mutation testing in the context of first-line treatment of NSCLC based on trials comparing an EGFR TKI to a platinum-based chemotherapy doublet Studies considered were limited to those comparing an EGFR TKI to chemotherapy, as the latter has been the standard of care for first-line treatment. The PCO addresses the role of EGFR mutation testing in selecting first-line treatment

©American Society of Clinical Oncology All rights reserved - PFS outcomes – included studies StudyAgent EGFR mutation test positive – months HR (95% CI) P value EGFR mutation test negative – months HR (95% CI) P value IPASS NEJM 2009 Annals Onc suppl 2010 JCO suppl 2009 gefitinib9.5 vs ( ) ¤ < vs ( ) ¤ < Lee et al. 13 th WCLC 2009 gefitinib8.4 vs ( )2.1 vs ( ) Maemondo et al. NEJM 2010 gefitinib10.8 vs ( ) <0.001 N/A Mitsudomi et al. Lancet Onc 2009 gefitinib9.2 vs ( ) <0.001 N/A Zhou et al. Annals Onc supp 2010 erlotinib13.1 vs ( ) < N/A Note: outcomes in bold reached statistical significance ¤ treatment by biomarker status interaction test p<0.001

©American Society of Clinical Oncology All rights reserved - Literature Review and Analysis The major impetus for the PCO was the publication by Mok et al. that reported the results of the Iressa Pan-Asia Study, or IPASS (NEJM 2009). ASCO asked the National Cancer Institute’s Physician Data Query (PDQ) Adult Cancer Editorial Board to conduct an assessment of this trial to inform the PCO.

©American Society of Clinical Oncology All rights reserved - Literature Review and Analysis: IPASS The Iressa Pan-Asia Study (IPASS) was a phase III, multicenter, randomized, open-label, parallel-group study comparing gefitinib with carboplatin plus paclitaxel as first-line treatment for patients in East Asia who had advanced adenocarcinoma of the lung and were nonsmokers or former light smokers with other specific clinical characteristics The primary outcome of interest was PFS and the trial was designed to show non-inferiority

©American Society of Clinical Oncology All rights reserved - Literature Review and Analysis: National Cancer Institute PDQ Editorial Review Assessment Upon request from ASCO, the National Cancer Institute’s PDQ Editorial Board provided a written assessment of the IPASS data ( board). board PDQ assessment of IPASS –met primary objective of demonstrating non-inferiority –showed superiority of gefitinib versus carboplatin– paclitaxel for PFS

©American Society of Clinical Oncology All rights reserved - Literature Review and Analysis: National Cancer Institute PDQ Editorial Review Assessment The assessment highlighted substantive points for the PCO ad hoc panel’s consideration: –The participants in IPASS were people from China, Japan, Korea, Thailand, and Taiwan –the applicability of these results to non-Asian populations with similar clinical or mutational features is uncertain –may be additional environmental or genotypic factors between populations that may alter sensitivity to therapy

©American Society of Clinical Oncology All rights reserved - Literature Review and Analysis: National Cancer Institute PDQ Editorial Review Assessment Highlighted substantive points for the PCO (cont’d) – The magnitude of benefit from erlotinib versus chemotherapy obtained in clinical trials testing gefitinib is not currently known when using erlotinib (the only EGFR TKI now approved in the United States) –Extrapolations from other analyses suggest possible comparability

©American Society of Clinical Oncology All rights reserved - Integrative Discussion and Analysis 5 RCTs included: 4/5 PFS statistically significant improvement for mutation positive patientstaking EGFR TKI 1 st -line EGFR TKI not beneficial for those testing negative for EGFR mutations PCO applies primarily to patients with adenocarcinoma POPULATIONS No significant differences in types and locations of EGFR mutations between NSCLC of Asians and non-Asians

©American Society of Clinical Oncology All rights reserved - Integrative Discussion and Analysis POPULATIONS All EGFR mutations in same loci of the DNA across ethnicities –Also true for secondary T790M and MET gene amplification Across reports of using EGFR TKIs for patients with positive mutations: –Similar overall response rates –Similar overall survival rates

©American Society of Clinical Oncology All rights reserved - Integrative Discussion and Analysis AGENTS Apparent similarly results for erlotinib and gefitinib from OPTIMAL (erlotinib) and IPASS (gefitinib) trials Awaiting additional results Extrapolating from erlotinib studies: Study of 2 nd /3 rd line erlotinib: positive mutation test higher response rates Study of maintenance: positive mutation test higher PFS

©American Society of Clinical Oncology All rights reserved - ASCO’s Provisional Clinical Opinion Based on the results of five phase III RCTs, patients with advanced non-small cell lung cancer of the lung who are being considered for first-line therapy with an EGFR TKI (patients who have not previously received chemotherapy or an EGFR TKI) should have their tumor tested for EGFR mutations to determine which is an appropriate first-line therapy: an EGFR TKI or chemotherapy.

©American Society of Clinical Oncology All rights reserved - Guideline Methodology: Update Committee Members Update Committee MembersAffiliation/Institution Giuseppe Giaccone, MD, Co-ChairNational Cancer Institute Vicki Leigh Keedy, MD, Co-ChairVanderbilt University Medical Center Mary Beth Beasley, MD, FACPMount Sinai Medical Center David H. Johnson, MD, FACPUniversity of Texas, Southwestern Medical Center Lisa M. McShane, PhDNational Cancer Institute Daniel T. Milton, MDHematology/Oncology of Indiana, PC John R. Strawn, MDPatient Representative Heather A. Wakelee, MDStanford University

©American Society of Clinical Oncology All rights reserved - Additional ASCO Resources The PCO and a patient guide can be found at: A patient guide, “What to Know” about this PCO, is also available at:

©American Society of Clinical Oncology All rights reserved - ASCO Guidelines This resource is a practice tool for physicians based on an ASCO® Provisional Clinical Opinion (PCO). The PCO and this presentation are not intended to substitute for the independent professional judgment of the treating physician. PCOs do not account for individual variation among patients and may not reflect the most recent evidence. This presentation does not recommend any particular product or course of medical treatment. Use of the PCO and this resource is voluntary. The full PCO and additional information are available at Copyright © 2011 by American Society of Clinical Oncology®. All rights reserved.