446P - Afatinib (A) versus chemotherapy (CT) for EGFR mutation-positive NSCLC patients (pts) aged ≥65 years: Subgroup analyses of LUX-Lung 3 (LL3) and LUX...

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, S.L. Geater3, S. Orlov4, K.H. Lee5, C. Tsai6, T. Kato7, K. Kiura8, C.H. Barrios9, M. Schuler10, V. Hirsh11, N. Yamamoto12, K. O'Byrne13, T. Mok14, D. Massey15, A. Märten16, J.C. Yang17
  • 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
  • 3Faculty Of Medicine, Prince of Songkla University, 90110 - Songkhla/TH
  • 4Department Of Thoracic Oncology, Pavlov State Medical University, Saint Petersburg/RU
  • 5Department Of Internal Medicine, Chungbuk National University Hospital, Cheong-ju/KR
  • 6Department Of Chest Medicine, Taipei Veterans General Hospital, Taipei/TW
  • 7Department Of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 2360051 - Yokohama/JP
  • 8University Hospital Of Medicine And Dentistry, Okayama University Hospital, Okayama/JP
  • 9Department Of Oncology, PUCRS School of Medicine, Porto Alegre/BR
  • 10West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen/DE
  • 11Department Of Oncology, McGill University, Montreal/CA
  • 12Third Department Of Internal Medicine, Wakayama Medical University, Wakayama/JP
  • 13Translational Research Institute, Princess Alexandra Hospital and Queensland University of Technology, Brisbane/AU
  • 14State Key Laboratory Of South China, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong/CN
  • 15Biometrics/clinical, Boehringer Ingelheim Ltd UK, Bracknell/GB
  • 16Ta Oncology, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Rheine/DE
  • 17Department Of Oncology, National Taiwan University Hospital and National Taiwan University, Taipei/TW

Abstract

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.