In the LL3 (345 pts recruited globally) and LL6 (364 Asian-only pts [no Japanese]) phase 3 randomized trials, first-line A, an irreversible ErbB family blocker, significantly improved OS vs cisplatin/pemetrexed (33.3 vs 21.1 months; HR 0.54; p = 0.0015) and gemcitabine/cisplatin (31.4 vs 18.4 months; HR 0.64; p = 0.023) in pts with advanced NSCLC harboring EGFR Del19 mut; no significant difference in OS was observed in EGFR L858R mut-positive patients in either study. Pre-planned subgroup analyses of OS by race including Asian, non-Asian (LL3 only), and Japanese patients (LL3 only) are reported.
In each study, pts were randomized (2:1) to 40 mg/day oral A or up to 6 cycles of CT, stratified by EGFR mut (Del19/L858R/other) and race (LL3 only; Asian/non-Asian).
Significant improvements in OS in NSCLC pts harboring EGFR Del19 mut were observed in all race subgroups analyzed. In the Asian subgroup of LL3, median OS in Del19 pts (n = 123) was 33.3 months with A vs 22.9 months with CT (HR 0.57 [95% CI 0.36–0.90]; p = 0.015). In the non-Asian subgroup of LL3, median OS in Del19 pts (n = 46) was 33.6 months with A vs 20.0 months with CT (HR 0.45 [95% CI 0.21–0.95]; p = 0.03). In the Japanese subgroup of LL3, median OS in Del19 pts (n = 39) was 46.9 months with A vs 31.5 months with CT (HR 0.34 [95% CI 0.13–0.87]; p = 0.018). Significant improvement in OS with A vs CT was also observed in the combined analysis of Asian Del19 pts (n = 309) in LL3 and LL6 (median 31.7 vs 21.1 months; HR 0.61 [95% CI 0.46–0.82]; p = 0.001). No statistically significant difference in OS with A vs CT was observed for L858R mut pts in any of the race subgroups analyzed. Subsequent EGFR tyrosine kinase inhibitor therapy was received by 69%, 65% and 100% of non-Asian, Asian and Japanese patients, respectively, in the CT arm.
Significant improvement in OS with first-line A vs CT in pts with NSCLC harboring EGFR Del19 mut was demonstrated in subgroup analyses of Asian, non-Asian, and Japanese pts. These findings are consistent with analysis of the overall LL3 and LL6 pooled population.
Clinical trial identification
Y.-L. Wu: honoraria from Boehringer Ingelheim, Roche, AstraZeneca, Eli Lilly and Pfizer. L.V. Sequist: advisory board involvement in an uncompensated role for Boehringer Ingelheim, AstraZeneca, Clovis, Novartis, Genetech, Merrimack, and Taiho. 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.
N. Yamamoto: advisory board involvement, corporate-sponsored research and honoraria with Boehringer Ingelheim. K. O'Byrne, V. Hirsh: honoraria for advisory board involvement with 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. V. Zazulina: employment with Boehringer Ingelheim. 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; and 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.