Afatinib (A) vs gefitinib (G) in patients (pts) with EGFR mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC): overall survival (OS) data from the phase IIb trial LUX-Lung 7 (LL7)

Background

The irreversible ErbB family blocker, A, and the reversible EGFR TKI, G, are approved for 1st-line treatment (tx) of advanced EGFRm+ NSCLC. In LL7, A (40 mg/d) significantly improved PFS (HR 0.73 [95% CI 0.57–0.95], p = 0.017), ORR (70 vs 56%, p = 0.008) and time to tx failure (TTF; HR 0.73 [0.58–0.92], p = 0.007) vs G (250 mg/d) in this setting. Here, we present primary analysis of mature OS data.

Methods

LL7 assessed A vs G in tx-naïve pts with stage IIIb/IV NSCLC and a Del19/L858R EGFR mutation. Co-primary endpoints were PFS, TTF and OS. Other endpoints included ORR and AEs. Primary OS analysis was planned after ∼213 OS events and follow-up of ≥32 mos.

Results

Events for OS analysis were met at the data cut-off of 8 Apr 2016. Median follow-up for OS: 42.6 mos. Median tx duration: 13.7 (A) vs 11.5 (G) mos. 73/77% (A/G) of pts had ≥1 subsequent systemic anti-cancer treatment after discontinuation of A/G. 46/56% (A/G) received a subsequent EGFR TKI; 20 (14%)/23 (15%) pts (A/G) received a 3rd-gen EGFR TKI. There was a trend towards improved OS with A vs G (median 27.9 vs 24.5 mos; HR 0.86 [0.66–1.12], p = 0.258). Landmark 24-mo and 30-mo OS rates were 61 vs 51% (A vs G) and 48 vs 40% (A vs G); these survival rates with A were similar to the LL3 trial (60 and 50% in pts with common EGFR mutations). Prespecified subgroup analyses showed similar OS trends with A vs G in pts with Del19 (30.7 vs 26.4 mos; HR 0.83 [0.58–1.17]) and L858R (25.0 vs 21.2 mos; HR 0.92 [0.62–1.36]) mutations. There was a trend towards improved OS with A vs G in pts who received a 3rd-gen EGFR TKI (NE vs 46.0 mos; HR 0.51 [0.17–1.52]). In pts treated with A, consistent OS outcomes were observed across age groups (median, mos: 27.9 [≥60 yrs]; 26.7 [≥65 yrs]; 25.1 [≥70 yrs]; 27.9 [≥75 yrs]). Updated PFS, TTF and ORR data were similar to the primary analyses; all were significantly improved with A vs G. The AE profile of A and G was virtually unchanged since the primary analysis.

Conclusions

In LL7, there was no significant difference in OS with A vs G. A trend favouring afatinib, generally consistent across subgroups, was observed. Updated analyses of PFS (independent), TTF and ORR all significantly favoured A over G.

Clinical trial identification

Clinical trial registration: NCT01466660

Legal entity responsible for the study

Boehringer Ingelheim

Funding

Boehringer Ingelheim

Disclosure

L. Zhang: Membership on advisory board/board of directors (AstraZeneca, Lilly). V. Hirsh: Membership on advisory board and honoraria (Boehringer Ingelheim). K. O'Byrne: Honoraria (Pfizer, Roche, AZD, Boehringer Ingelheim, BMS, MSD, Lilly, Novartis); advisory role (Pfizer, Roche, AZD, Boehringer Ingelheim, BMS, MSD, Lilly, Novartis); speaker's bureau (Pfizer, Roche, AZD, Boehringer Ingelheim, MSD, Lilly); travel/accommodation expenses (Roche, AZD, Boehringer Ingelheim, MSD); stock (CARP Pharmaceuticals, Bluesky Biosciences); Patents (TCD Ref LO02-310-01, Australian Provisional Patent 2015905380). M. Boyer: Membership on advisory board or board or directors (AstraZeneca); corporate-sponsored research (AstraZeneca, Boehringer Ingelheim, Clovis, Roche). J.C-H. Yang: Membership on advisory board or board of directors (Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, AstraZeneca, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, innopharma, Merrimack). 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). J. Fan, A. Märten: Employment (Boehringer Ingelheim). K. Park: Membership on advisory board (Boehringer Ingelheim); corporate-sponsored research (AstraZeneca). All other authors have declared no conflicts of interest.