An afatinib NPU program started in 2010 after the Phase 2b/3 LUX-Lung 1 trial demonstrated significantly improved progression-free survival and objective response rate (ORR) with afatinib versus placebo in advanced NSCLC patients following failure of E/G and 1–2 lines of chemotherapy.
Eligible advanced NSCLC patients had either progressed after clinical benefit on prior E/G and/or had an activating EGFR/HER2 mutation; had exhausted all other treatments; and were ineligible for afatinib trials. Time to treatment failure (TTF) was defined as the time from drug start to the date of treatment discontinuation.
Data as of January 2016 from 3966 NSCLC patients from 41 countries (6 continents) are reported here. Patients were heavily pretreated, with approximately 50% receiving afatinib as ≥4th-line treatment. Among the 65.4% (n = 2595/3966) of patients with known tumour EGFR status, 92.8% were EGFR mutation-positive. Median TTF for afatinib was calculated for 2862/3966 patients (72.2%) based on available data. TTF was 4.4 months for all patients, similar to the TTF for patients reported as EGFR mutation-positive, or as harbouring either common or uncommon EGFR mutations (each 4.3 months). For patients with response assessments reported (n = 1141/2862; 39.9%), the ORR was 23% (267/1141) for all patients and 25% (181/723) for those with NSCLC harbouring any EGFR mutation. Notably, a 26% (26/100) ORR was reported in patients with NSCLC harbouring uncommon EGFR mutations, including 19% (11/58) in T790M mutation-positive patients and 35% (7/20) in those with insertions in exon 20. No new/unexpected safety findings were observed
This afatinib NPU program in ∼4000 NSCLC patients who were refractory to several therapies, including prior E/G, revealed encouraging TTF durations and ORR. The afatinib safety profile was as anticipated.
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F. Cappuzzo: Membership on advisory board or board of directors (Roche, AstraZeneca, BMS, Pfizer). R. Soo: Membership on advisory board or board of directors (AstraZeneca, Boehringer Ingelheim, Lilly, Merck, Novartis, Pfizer, Roche). M. Schuler: Membership on advisory board/board of directors (AZ, BI, BMS, Celgene, IQWig, Lilly, Novartis); corporate-sponsored research (BI, BMS, Novartis); lecture fees (Alexion, BI, Celgene, GSK, Lilly, Novartis); patents (University Duisburg-Essen). T.S.K. Mok: Stock (Sanomics Ltd); advisory board (AZ, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Janssen, Clovis Oncology, BioMarin, GSK, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Inc., Vertex Pharmaceuticals, Aveo & Biodesix, BMS, geneDecode Co., Ltd, OncoGenex Technologies Inc.); board of directors (IASLC, Chinese Lung Cancer Research Foundation Ltd, CSCO, HKCTS); corporate-sponsored research (AZ, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS). G. Stehle: Employment and patent/royalty/other intellectual property (Boehringer Ingelheim). A. Cseh: Employment (Boehringer Ingelheim); stock (MEDA). R.M. Lorence: Employment and consulting/advisory role (Boehringer Ingelheim). S. Linden: Employment (Boehringer Ingelheim). N.D. Forman: Employment (Boehringer Ingelheim); stock/other ownership (INSYS Therapeutics). C-M. Tsai: Honoraria (Pfizer, Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca). All other authors have declared no conflicts of interest.