Nieuwe patiëntenselectie met longcarcinoom als role model voor de medisch oncoloog Anne-Marie Dingemans, longarts Dingemans | 19 juni 2014 2 Disclosure belangen spreker (potentiële) belangenverstrengeling Zie hieronder Voor bijeenkomst mogelijk relevante relaties met bedrijven Bedrijfsnamen Sponsoring of onderzoeksgeld Honorarium of andere (financiële) vergoeding Roche Eli Lilly Boehringer Ingelheim Astra Zeneca Pfizer BMS Amgen Astra Zeneca Novartis Dingemans | 19 juni 2014 “oncogene addiction” Sharma 2006 3 Dingemans | 19 juni 2014 4 Dingemans | 19 juni 2014 5 Dingemans | 19 juni 2014 Role model: zoek het doel 6 Dingemans | 19 juni 2014 SQUIRE Presented By Nick Thatcher at 2014 ASCO Annual Meeting 7 Dingemans | 19 juni 2014 Objectives & Statistical Assumptions Presented By Nick Thatcher at 2014 ASCO Annual Meeting 8 Dingemans | 19 juni 2014 Slide 9 Presented By Nick Thatcher at 2014 ASCO Annual Meeting 9 Dingemans | 19 juni 2014 10 Exploratory Analysis: <br />EGFR H-Score at 200 Cutpoint* Presented By Nick Thatcher at 2014 ASCO Annual Meeting Dingemans | 19 juni 2014 Necitumumab in SQ Positieve studie Geen biomarker (H-score voorspelt niet) Klein verschil ≈ FLEX Toekomst? 12 Dingemans | 19 juni 2014 13 JCO, 2014 Dingemans | 19 juni 2014 14 Vóór ASCO 2014 geregistreerd voor longkanker EGFR-mutatie (10%) -erlotinib/gefitinib/afatinib EML4-ALK translokatie (4%) -crizotinib na eerste lijns chemotherapie Dingemans | 19 juni 2014 Nieuwe middelen ASCO 2014 EGFR ALK ROS MET En hoe vind je de targets 15 Dingemans | 19 juni 2014 Nieuwe middelen ASCO 2014 EGFR: driver in 10% ALK ROS MET En hoe vind je de targets 16 Dingemans | 19 juni 2014 17 1st ESMO Consensus Conference in Lung Cancer: Lugano 2010 Felip, et al. Ann Oncol 2011 Dingemans | 19 juni 2014 Effect of Mutations on the Signaling Pathway Sequist L et al. N Engl J Med 2008;359:405-414 18 Dingemans | 19 juni 2014 Presented By Thomas Lynch at 2014 ASCO Annual Meeting 19 Dingemans | 19 juni 2014 CO-1686: mediane PFS > 12 maanden! Presented By Lecia Sequist at 2014 ASCO Annual Meeting 20 Dingemans | 19 juni 2014 ASCO daily evening news 21 Dingemans | 19 juni 2014 Preliminary Efficacy Comparison Presented By Thomas Lynch at 2014 ASCO Annual Meeting 22 Dingemans | 19 juni 2014 Toxicity Comparison Presented By Thomas Lynch at 2014 ASCO Annual Meeting 23 Dingemans | 19 juni 2014 Next generation EGFR-TKI Veel belovend, mn bij T790M+ Minder bijwerkingen Eerste lijn? 24 Dingemans | 19 juni 2014 25 Dingemans | 19 juni 2014 8017: Gefitinib and INC280 in <br />EGFR mut + acquired resistance 26 Dingemans | 19 juni 2014 8017: Efficacy in MET highest pts 27 Dingemans | 19 juni 2014 Resistentie EGFR-TKI Test MET / T790M: +? STUDIE Geen T790M: ook EGFR-TKI doorgeven 28 Dingemans | 19 juni 2014 Nieuwe middelen na ASCO 2014 EGFR ALK: 4% ROS MET En hoe vind je de targets 29 Dingemans | 19 juni 2014 30 Crizotinib: expanded cohort fase I Kwak, NEJM 2010 Dingemans | 19 juni 2014 PROFILE 1014 Study Design 31 Dingemans | 19 juni 2014 Primary Endpoint Met: Crizotinib Superior to Pemetrexed-based Chemotherapy in Prolonging PFSa 32 Dingemans | 19 juni 2014 33 7504: Analysis of resistance mechanisms to ALK kinase inhibitors in ALK positive NSCLC patients – Doebele RC et al ALK Non-Dominant ALK Dominant Doebele. JCO 30, 2012 (suppl; 7504) Dingemans | 19 juni 2014 Ceritinib in Advanced Anaplastic Lymphoma Kinase Rearranged (ALK+) Non-small Cell Lung Cancer (NSCLC) – Results of the ASCEND-1 Trial (#8003) Presented By Dong-Wan Kim at 2014 ASCO Annual Meeting 34 Dingemans | 19 juni 2014 ASCEND-1 Study Design Presented By Dong-Wan Kim at 2014 ASCO Annual Meeting 35 Dingemans | 19 juni 2014 Best Percentage Change from Baseline (NSCLC) Presented By Dong-Wan Kim at 2014 ASCO Annual Meeting 36 Dingemans | 19 juni 2014 Progression-Free Survival in Patients with ALK+ NSCLC Presented By Dong-Wan Kim at 2014 ASCO Annual Meeting 37 Dingemans | 19 juni 2014 59% minstens 1 dosis reductie Presented By Dong-Wan Kim at 2014 ASCO Annual Meeting 38 Dingemans | 19 juni 2014 ALK remmers Crizotinib = eerste lijns keuze Ceritinib: ACTIEF! Maar cave toxiciteit • 1ste/2de lijn 39 Dingemans | 19 juni 2014 Nieuwe middelen na ACO 2014 EGFR ALK ROS: 2% MET En hoe vind je de targets 40 Dingemans | 19 juni 2014 Efficacy of crizotinib in ROS1-rearranged lung cancer: the European experience (EUROS1 cohort). 41 Dingemans | 19 juni 2014 Results (2) 42 Dingemans | 19 juni 2014 BMJ 2006 43 Dingemans | 19 juni 2014 Nieuwe middelen na ASCO 2014 EGFR ALK ROS MET En hoe vind je de targets 44 Dingemans | 19 juni 2014 The two faces of MET Presented By Federico Cappuzzo at 2014 ASCO Annual Meeting 45 Dingemans | 19 juni 2014 46 MET Pathway Presented By D. Camidge at 2014 ASCO Annual Meeting Dingemans | 19 juni 2014 MET deregulation in lung cancer Presented By Federico Cappuzzo at 2014 ASCO Annual Meeting 47 Dingemans | 19 juni 2014 48 MET is amplified in a subset of <br />lung cancers Presented By D. Camidge at 2014 ASCO Annual Meeting Dingemans | 19 juni 2014 49 Expansion cohort fase I crizotinib Presented By D. Camidge at 2014 ASCO Annual Meeting Dingemans | 19 juni 2014 The two faces of MET Presented By Federico Cappuzzo at 2014 ASCO Annual Meeting 50 Dingemans | 19 juni 2014 Targeting MET and EGFR – reduction in tumor cell proliferation and survival Presented By David Spigel at 2014 ASCO Annual Meeting 51 Dingemans | 19 juni 2014 Phase 2 Results (OAM4558g): MET IHC Status may Predict Clinical Benefit from Onartuzumab + Erlotinib Presented By David Spigel at 2014 ASCO Annual Meeting 52 Dingemans | 19 juni 2014 Global Phase 3 Trial (METLung)* of Onartuzumab plus Erlotinib in NSCLC: Trial Design Presented By David Spigel at 2014 ASCO Annual Meeting 53 Dingemans | 19 juni 2014 OAM4971g: Overall Survival Results Presented By David Spigel at 2014 ASCO Annual Meeting 54 Dingemans | 19 juni 2014 OAM4971g: Progression-Free Survival Presented By David Spigel at 2014 ASCO Annual Meeting 55 Dingemans | 19 juni 2014 Conclusions Presented By Federico Cappuzzo at 2014 ASCO Annual Meeting 56 Dingemans | 19 juni 2014 Nieuwe middelen EGFR ALK ROS MET En hoe vind je de targets 57 Dingemans | 19 juni 2014 58 <br /><br />Next-generation sequencing (NGS) to identify actionable genomic alterations in “pan-negative” lung adenocarcinomas from patients with no smoking or a light smoking history Dingemans | 19 juni 2014 Slide 3 59 Dingemans | 19 juni 2014 Results 60 Dingemans | 19 juni 2014 Nieuwe middelen na ASCO 2014 EGFR: necitumimab? / 3de generatie specifieke remmers ALK: crizotinib/ceritinib ROS: crizotinib MET amplificatie: crizotinib Geen target? NGS 61 Dingemans | 19 juni 2014 62 Dingemans | 19 juni 2014 63
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