Yi-Long Wu1, Lecia V Sequist2, Eng-Huat Tan3, Sarayut L Geater4, Sergey Orlov5, Li Zhang6, Ki Hyeong Lee7, Chun-Ming Tsai8, Terufumi Kato9, Carlos H Barrios10, Martin Schuler11, Vera Hirsh12, Nobuyuki Yamamoto13, Kenneth O'Byrne14, Michael Boyer15, Tony Mok16, Barbara Peil17, Angela Märten17, James Chih-Hsin Yang18, Luis Paz-Ares19, Keunchil Park20. 1. Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: syylwu@live.cn. 2. Department of Thoracic Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA. 3. Division of Medical Oncology, National Cancer Centre, Singapore, Singapore. 4. Department of Internal Medicine, Prince of Songkla University, Songkhla, Thailand. 5. Department of Thoracic Oncology, Pavlov State Medical University, St Petersburg, Russia. 6. Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China. 7. Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea. 8. Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan. 9. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. 10. Department of Internal Medicine, PUCRS School of Medicine, Porto Alegre, Rio Grande do Sul, Brazil. 11. Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany. 12. Faculty of Medicine/Oncology, McGill University, Montréal, Quebec, Canada. 13. Wakayama Medical University, Wakayama, Wakayama Prefecture, Japan. 14. Department of Medical Oncology, Princess Alexandra Hospital and Queensland University of Technology, Brisbane, Queensland, Australia. 15. Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. 16. Department of Clinical Oncology, State Key Laboratory of South China, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China. 17. Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany. 18. Department of Oncology, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan. 19. Department of Lung Cancer, Hospital Universitario Doce de Octubre, Universidad Complutense, CiberOnc and CNIO, Madrid, Spain. 20. Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Abstract
BACKGROUND:Afatinib is approved in the US, Europe, and several other regions for first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Treatment-naive patients with advanced EGFRm+ NSCLC were randomized to afatinib (40 mg/d) versus cisplatin/pemetrexed (LUX-Lung 3 [LL3]) or cisplatin/gemcitabine (LUX-Lung 6 [LL6]), or versus gefitinib (250 mg/d; LUX-Lung 7 [LL7]). We report subgroup analyses according to age, including 65 years or older versus younger than 65 years (preplanned; LL3/LL6) and additional cutoffs up to 75 years and older (exploratory; LL7). Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. RESULTS: Among the 134 of 345 (39%) and 86 of 364 (24%) patients aged 65 years and older in LL3 and LL6, median PFS was improved with afatinib versus chemotherapy (LL3: hazard ratio [HR], 0.64 [95% confidence interval (CI), 0.39-1.03]; LL6: HR, 0.16 [95% CI, 0.07-0.39]). Afatinib significantly improved OS versus chemotherapy in elderly patients with Del19+ NSCLC in LL3 (HR, 0.39 [95% CI, 0.19-0.80]). Among the 40 of 319 patients (13%) aged 75 years or older in LL7, median PFS (HR, 0.69 [95% CI, 0.33-1.44]) favored afatinib, consistent with the overall population. Afatinib-associated AEs in older patients were consistent with the overall populations. CONCLUSIONS: Subgroup analyses of the LL3, LL6, and LL7 trials show that afatinib is an effective and tolerable treatment for patients with EGFRm+ NSCLC, independent of age.
RCT Entities:
BACKGROUND:Afatinib is approved in the US, Europe, and several other regions for first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Treatment-naive patients with advanced EGFRm+ NSCLC were randomized to afatinib (40 mg/d) versus cisplatin/pemetrexed (LUX-Lung 3 [LL3]) or cisplatin/gemcitabine (LUX-Lung 6 [LL6]), or versus gefitinib (250 mg/d; LUX-Lung 7 [LL7]). We report subgroup analyses according to age, including 65 years or older versus younger than 65 years (preplanned; LL3/LL6) and additional cutoffs up to 75 years and older (exploratory; LL7). Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. RESULTS: Among the 134 of 345 (39%) and 86 of 364 (24%) patients aged 65 years and older in LL3 and LL6, median PFS was improved with afatinib versus chemotherapy (LL3: hazard ratio [HR], 0.64 [95% confidence interval (CI), 0.39-1.03]; LL6: HR, 0.16 [95% CI, 0.07-0.39]). Afatinib significantly improved OS versus chemotherapy in elderly patients with Del19+ NSCLC in LL3 (HR, 0.39 [95% CI, 0.19-0.80]). Among the 40 of 319 patients (13%) aged 75 years or older in LL7, median PFS (HR, 0.69 [95% CI, 0.33-1.44]) favored afatinib, consistent with the overall population. Afatinib-associated AEs in older patients were consistent with the overall populations. CONCLUSIONS: Subgroup analyses of the LL3, LL6, and LL7 trials show that afatinib is an effective and tolerable treatment for patients with EGFRm+ NSCLC, independent of age.
Authors: Antonio Passaro; Filippo de Marinis; Hai-Yan Tu; Konstantin K Laktionov; Jifeng Feng; Artem Poltoratskiy; Jun Zhao; Eng Huat Tan; Maya Gottfried; Victor Lee; Dariusz Kowalski; Cheng Ta Yang; B J Srinivasa; Laura Clementi; Tejaswini Jalikop; Dennis Chin Lun Huang; Agnieszka Cseh; Keunchil Park; Yi-Long Wu Journal: Front Oncol Date: 2021-07-09 Impact factor: 6.244