Afatinib (A) versus chemotherapy (CT) for EGFR mutation-positive NSCLC patients (pts) aged >= 65 years: Subgroup analyses of LUX-Lung 3 (LL3) and LUX-Lung 6 (LL6)

Aim/Background: First-line A significantly improved progression-free survival (PFS) vs CT in pts with EGFR mutation-positive NSCLC in the LL3 and LL6 trials (LL3: 11.1 vs 6.9 months, HR 0.58; p < 0.001; LL6: 11.0 vs 5.6 months, HR 0.28; p < 0.0001). Overall survival (OS) was significantly improved with A vs CT in pts with Del19 mutations (LL3: 33.3 vs 21.1 months, HR 0.54, p = 0.0015; LL6: 31.4 vs 18.4 months, HR 0.64, p = 0.023). The efficacy and safety of A vs CT in pts aged ≥65 years in the LL3 and LL6 trials are reported. Methods: Pts with EGFR mutation-positive stage IIIB or IV NSCLC (345 in LL3 and 364 in LL6) were randomized 2:1 to oral A (40 mg/day) or up to 6 cycles of CT (LL3: cisplatin/pemetrexed; LL6: cisplatin/gemcitabine). Pts were stratified by EGFR mutation (Del19/L858R/other) and race (LL3 only; Asian/non-Asian). Analyses by age (<65, ≥65) were pre-specified for both trials, analyses by age within mutation subgroups were post-hoc. Results: In LL3 and LL6, 134 and 86 pts aged ≥65 years, respectively, were randomized. PFS was significantly improved with A vs CT in these pts (LL3: 13.6 vs 8.2 months, HR 0.60 [95% CI 0.37–0.96], p = 0.03; LL6: 13.1 vs 4.1 months, HR 0.17 [95% CI 0.07–0.41], p < 0.0001). OS was similar with A vs CT in all pts aged ≥65 years, with a trend towards improved OS with A vs CT noted in those with common EGFR mutations (LL3: 31.6 vs 24.9 months; HR 0.73 [95% CI 0.43–1.21], p = 0.22; LL6: 23.2 vs 19.0 months, HR 0.60 [95% CI 0.33–1.10], p = 0.10). In pts aged ≥65 years with Del19 mutations, OS was significantly improved with A vs CT in LL3 (41.5 vs 14.3 months; HR 0.39 [95% CI 0.19–0.80]; p = 0.0073) with a trend towards improved OS in LL6 (34.1 vs 21.1 months; HR 0.57 [95% CI 0.24–1.36]; p = 0.20). Across the trials, the most common treatment-related grade 3/4 adverse events (AEs) in A-treated pts aged ≥65 years were diarrhea (21% in LL3 and 8% in LL6), rash/acne (19% and 9%), nail effects (16% LL3 only) and stomatitis (10% and 3%). Conclusions: Consistent with the overall population, A conferred substantial clinical benefit vs CT in pts aged ≥65 years, with improved OS in those with Del19 mutations. The AE profile was similar to that observed in the overall population. Clinical trial identification: NCT00949650; NCT01121393 Disclosure: Y.-L. Wu: honoraria from BI, Roche, AstraZeneca, Eli Lilly, and Pfizer. L.V. Sequist: uncompensated advisory board participation for Boehringer Ingelheim, AstraZeneca, Clovis, Novartis, Genentech, Merrimack, and Taiho. S.L. Geater: employment at the Prince of Songkla University; advisory board participation at Boehringer Ingelheim; institutional research funds from Boehringer Ingelheim, Astrazeneca, Roche, Teva Pharmaceuticals, and Eisai; honoraria from Boehringer Ingelheim, Roche, and AstraZeneca. C.-M. Tsai: honoraria from Pfizer, Roche, Eli Lilly, Boehringer Ingelheim, and AstraZeneca. T. Kato: corporate-sponsored research for, and honoraria from, Boehringer Ingelheim. K. Kiura: corporate-sponsored research for Boehringer Ingelheim; and honoraria from Lilly, Chugai, Boehringer Ingelheim, AstraZeneca, and Astellas. C.H. Barrios: advisory board participation for Boehringer Ingelheim; corporate-sponsored research for Boehringer Ingelheim; and honoraria from Boehringer Ingelheim. M. Schuler: advisory board participation for AstraZeneca, Boehringer Ingelheim, Celgene, Lilly and Novartis; corporate-sponsored research for Boehringer Ingelheim and Novartis; and honoraria from Alexion, Boehringer Ingelheim, Celgene, Lilly, Novartis and Pfizer. V. Hirsh: honoraria for advisory board participation for Boehringer Ingelheim. N. Yamamoto: advisory board participation for Boehringer Ingelheim; corporate-sponsored research for Boehringer Ingelheim; and honoraria from Boehringer Ingelheim. K. O'Byrne: advisory board participation for Boehringer Ingelheim; and honoraria from Boehringer Ingelheim. T. Mok: Speaker's Bureau participant with AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, MSD, Amgen, Janssen, Clovis Oncology, GSK, and Novartis; advisory board participation for AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Janssen, Clovis Oncology, BioMarin, GSK, Novartis, SFJ Pharmaceutical, and ACEA Biosciences, Inc.; honoraria from AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Amgen, Janssen, Clovis Oncology, GSK, and Novartis; and major stock shareholder in Sanomics Ltd. D. Massey, A. Märten: employment by Boehringer Ingelheim Ltd. J.C.-H. Yang: advisory board participation for Astrazeneca, Roche/Genentech, Boehringer Ingelheim, MSD, Merck Serono, Novartis, Clovis Oncology, Eli Lilly, Bayer, Celgene, Astellas, Innopharma, and Ono Pharmaceutical; honoraria from Astrazeneca, Roche/Genentech, Boehringer Ingelheim, MSD, Merck Serono, Novartis, Clovis Oncology, Eli Lilly, Bayer, Celgene, Astellas, Innopharma, and Ono Pharmaceutical. All other authors have declared no conflicts of interest.