ACTIVITY OF AFATINIB/CETUXIMAB IN PATIENTS (PTS) WITH EGFR MUTANT NON-SMALL CELL LUNG CANCER (NSCLC) AND ACQUIRED RESISTANCE (AR) TO EGFR INHIBITORS

摘要: ABSTRACT Background AR to reversible epidermal growth factor receptor (EGFR)-specific tyrosine kinase inhibitors (TKIs) in EGFR mutant (mt) NSCLC is associated with an exon 20 T790M mutation ∼50% of cases. The targeted combination afatinib (A), a potent ErbB Family Blocker, and cetuximab (C), induced nearly complete regression transgenic murine models. Following determination the maximum tolerated dose, early clinical data suggest that recommended dose A/C tolerable, encouraging activity cases (Janjigian Y. J Clin Oncol 2011; 29 (suppl); abstr 7525). Here, we report safety efficacy from expanded cohort NSCLC. Methods Pts mt advanced – progressive on erlotinib or gefitinib transitioned directly (interval minimum 3 days) oral, daily A 40 mg intravenous, bi-weekly C 500 mg/m2. Tumour biopsy after AR, prior study therapy, was mandated by protocol. Efficacy endpoints included objective response (OR) progression-free survival (PFS) imaging at week 4, 8, 12 every 8 weeks thereafter. Results To date, 100 eligible pts have been treated (median duration 4.1 months, range 1–14+ months). del 19 L858R were present 63% 31% pts, 53% pts. Adverse events rash (Grade 1/2: 65%; Grade 3: 12%) diarrhoea 63%; 6%). Ninety evaluable for efficacy; rate disease control 94% probability PFS 3, 6 9 months 70, 42 18%, respectively. In first 60 enrolled least before cut-off, confirmed OR 40% (95% CI: 27.6–53.5), similar both T790M+ (38%) T790M- (47%) tumours; median 4.7 7.7 months. Conclusions Afatinib/cetuximab shows gefitinib, demonstrating many NSCLCs continue depend signalling survival. Efforts elucidate underlying mechanisms are ongoing, updated will be presented. Further studies planned establish potential role this treatment Disclosure Y.Y. Janjigian: Research funding Boehringer Ingelheim, INC. L. Horn: Unpaid advisory board OSI/Astellas/Genentech. H.J.M. Groen: Roche Eli Lilly University Medical Centre. D.R. Camidge: Consultancy honoraria BI; Lilly. Fu: Employee Ingelheim. L.J. Denis: V. Miller: Foundation Medicine-employment, stockholder. W. Pao: Consulting: MolecularMD, AstraZeneca, BMS, Symphony Evolution, Clovis Oncology; funding: Enzon, Xcovery, Symphogen, Other: Rights testing licensed behalf self others MSKCC MolecularMD. All other authors declared no conflicts interest.