445P - Overall survival (OS) with afatinib (A) vs chemotherapy (CT) in patients (pts) with NSCLC harboring EGFR mutations (mut): Subgroup analyses by race...

Date 20 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 2
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Yi-Long Wu
Citation Annals of Oncology (2015) 26 (suppl_9): 125-147. 10.1093/annonc/mdv532
Authors Y. Wu1, L.V. Sequist2, M. Schuler3, N. Yamamoto4, C. Zhou5, C. Hu6, K. O'Byrne7, V. Hirsh8, T. Mok9, V. Zazulina10, J.C. Yang11
  • 1Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 510080 - Guangzhou/CN
  • 2Department Of Thoracic Oncology, Massachusetts General Hospital and Harvard Medical School, Boston/US
  • 3West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen/DE
  • 4Third Department Of Internal Medicine, Wakayama Medical University, Wakayama/JP
  • 5Shanghai Pulmonary Hospital, Tongji University, Shanghai/CN
  • 6Xiangya Hospital, Central South University, Changsha/CN
  • 7Translational Research Institute, Princess Alexandra Hospital and Queensland University of Technology, Brisbane/AU
  • 8Department Of Oncology, McGill University, Montreal/CA
  • 9State Key Laboratory Of South China, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong/CN
  • 10Medical, Boehringer Ingelheim Ltd UK, Bracknell/GB
  • 11Department Of Oncology, National Taiwan University Hospital and National Taiwan University, Taipei/TW

Abstract

Aim/Background

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.

Methods

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).

Results

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.

Conclusions

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

NCT00949650; NCT01121393

Disclosure

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.