Martin Schuler1, Luis Paz-Ares2, Lecia V Sequist3, Vera Hirsh4, Ki Hyeong Lee5, Yi-Long Wu6, Shun Lu7, Caicun Zhou8, Jifeng Feng9, Stuart H Ellis10, Carl H Samuelsen11, Wenbo Tang12, Angela Märten13, Eva Ehrnrooth14, Keunchil Park15, James Chih-Hsin Yang16. 1. West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany. Electronic address: Martin.Schuler@uk-essen.de. 2. Hospital Universitario Doce de Octubre, CiberOnc, Universidad Complutense and CNIO, Madrid, Spain. Electronic address: lpazaresr@seom.org. 3. Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: lvsequist@partners.org. 4. McGill University, Montreal, Canada. Electronic address: vera.hirsh@muhc.mcgill.ca. 5. Chungbuk National University Hospital, Cheongju, South Korea. Electronic address: kihlee@chungbuk.ac.kr. 6. Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: syylwu@live.cn. 7. Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: shun_lu@hotmail.com. 8. Shanghai Pulmonary Hospital, Shanghai, China. Electronic address: caicunzhoudr@163.com. 9. Jiangsu Provincial Tumor Hospital, Nanjing, Jiangsu, China. Electronic address: fjif@vip.sina.com. 10. Independent Statistical Consultant, Cheshire, UK. Electronic address: stuart.ellis@n-zero-1.co.uk. 11. Boehringer Ingelheim International GmbH, Ingelheim, Germany. Electronic address: carl.samuelsen@boehringer-ingelheim.com. 12. Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. Electronic address: wenbo.tang@boehringer-ingelheim.com. 13. Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. Electronic address: angela.maerten@boehringer-ingelheim.com. 14. Boehringer Ingelheim, Danmark A/S, Denmark. Electronic address: evae@oncology.dk. 15. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: kpark@skku.edu. 16. National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan. Electronic address: chihyang@ntu.edu.tw.
Abstract
OBJECTIVES: In patients with advanced epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC), first-line afatinib significantly improved progression-free survival (PFS) and objective response vs. platinum-doublet chemotherapy in the phase III LUX-Lung 3 and LUX-Lung 6 trials, and significantly improved PFS, time to treatment failure and objective response vs. gefitinib in the phase IIb LUX-Lung 7 trial. We report post-hoc analyses of efficacy, safety and patient-reported outcomes (PROs) in afatinib long-term responders (LTRs) in these trials. METHODS:Treatment-naïve patients with stage IIIB/IV EGFRm + NSCLC randomized to afatinib in LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 were included in the analysis. Patients treated with afatinib for ≥ 3 years were defined as LTRs. RESULTS: In LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7, 24/229 (10%), 23/239 (10%) and 19/160 (12%) afatinib-treated patients were LTRs. Baseline characteristics were similar to the study populations, except for the proportions of women (LUX-Lung 3/LUX-Lung 6 only; 92/78% vs. 64% overall) and Del19-positive patients (63-79% vs. 49-58% overall). Median treatment duration among LTRs was 50, 56 and 42 months, and median PFS was 49.5, 55.5, and 42.2 months in LUX-Lung 3/LUX-Lung 6/LUX-Lung 7, respectively. Median overall survival could not be estimated. Frequency of afatinib dose reduction was consistent with the LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 overall populations. PROs were stable in LTRs, with slight improvements after 3 years of afatinib treatment vs. baseline scores. CONCLUSIONS: In the LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 trials, 10-12% of afatinib-treated patients were LTRs. Long-term afatinib treatment was independent of tolerability-guided dose adjustment and had no detrimental impact on safety or PROs.
RCT Entities:
OBJECTIVES: In patients with advanced epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC), first-line afatinib significantly improved progression-free survival (PFS) and objective response vs. platinum-doublet chemotherapy in the phase III LUX-Lung 3 and LUX-Lung 6 trials, and significantly improved PFS, time to treatment failure and objective response vs. gefitinib in the phase IIb LUX-Lung 7 trial. We report post-hoc analyses of efficacy, safety and patient-reported outcomes (PROs) in afatinib long-term responders (LTRs) in these trials. METHODS: Treatment-naïve patients with stage IIIB/IV EGFRm + NSCLC randomized to afatinib in LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 were included in the analysis. Patients treated with afatinib for ≥ 3 years were defined as LTRs. RESULTS: In LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7, 24/229 (10%), 23/239 (10%) and 19/160 (12%) afatinib-treated patients were LTRs. Baseline characteristics were similar to the study populations, except for the proportions of women (LUX-Lung 3/LUX-Lung 6 only; 92/78% vs. 64% overall) and Del19-positive patients (63-79% vs. 49-58% overall). Median treatment duration among LTRs was 50, 56 and 42 months, and median PFS was 49.5, 55.5, and 42.2 months in LUX-Lung 3/LUX-Lung 6/LUX-Lung 7, respectively. Median overall survival could not be estimated. Frequency of afatinib dose reduction was consistent with the LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 overall populations. PROs were stable in LTRs, with slight improvements after 3 years of afatinib treatment vs. baseline scores. CONCLUSIONS: In the LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 trials, 10-12% of afatinib-treated patients were LTRs. Long-term afatinib treatment was independent of tolerability-guided dose adjustment and had no detrimental impact on safety or PROs.
Authors: Tuo Zhang; Beibei Sun; Chenxi Zhong; Ke Xu; Zhexin Wang; Paul Hofman; Tatsuya Nagano; Antoine Legras; Daniel Breadner; Biagio Ricciuti; Duilio Divisi; Ralph A Schmid; Ren-Wang Peng; Haitang Yang; Feng Yao Journal: Transl Lung Cancer Res Date: 2021-04