Keunchil Park1, Jaafar Bennouna2, Michael Boyer3, Toyoaki Hida4, Vera Hirsh5, Terufumi Kato6, Shun Lu7, Tony Mok8, Kazuhiko Nakagawa9, Kenneth O'Byrne10, Luis Paz-Ares11, Martin Schuler12, Denis Moro Sibilot13, Eng-Huat Tan14, Hiroshi Tanaka15, Yi-Long Wu16, James C-H Yang17, Li Zhang18, Caicun Zhou19, Angela Märten20, Wenbo Tang21, Nobuyuki Yamamoto22. 1. Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, South Korea. Electronic address: kpark@skku.edu. 2. Department of Pneumology, Thoracic Oncology, University Hospital of Nantes, Boulevard Jacques-Monod Saint-Herblain, 44093, Nantes, France. Electronic address: jaafar.bennouna@univ-nantes.fr. 3. Department of Oncology, Chris O'Brien Lifehouse, 119-143 Missenden Road, Camperdown, NSW, 2050, Australia. Electronic address: michael.boyer@lh.org.au. 4. Aichi Cancer Center, 1-1 Kanokoden, Chikusa Ward, Nagoya, Aichi Prefecture, 464-8681, Japan. Electronic address: 107974@aichi-cc.jp. 5. Department of Oncology, McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC, H4A 3J1, Canada. Electronic address: vera.hirsh@muhc.mcgill.ca. 6. Kanagawa Cancer Center, 2 Chome-3-２ Nakao, Asahi Ward, Yokohama, Kanagawa Prefecture, 241-8515, Japan. Electronic address: terufumikato@gmail.com. 7. Department of Shanghai Lung Cancer, Shanghai Chest Hospital, Jiao Tong University Shanghai, China. Electronic address: shun_lu@hotmail.com. 8. Department of Clinical Oncology, The Chinese University of Hong Kong, LG, LKS Specialist Clinic (North Wing), Prince of Wales Hospital, Sha Tin, N.T., Hong Kong, China. Electronic address: tony@clo.cuhk.edu.hk. 9. Department of Medical Oncology, Kindai University Faculty of Medicine, Ohnohigashi 377-2, Osakasayama, Osaka Prefecture, 589-8511, Japan. Electronic address: nakagawa@med.kindai.ac.jp. 10. Department of Oncology, Princess Alexandra Hospital and Queensland University of Technology, 199 Ipswich Rd, Woolloongabba, QLD, 4102, Australia. Electronic address: k.obyrne@qut.edu.au. 11. Universitario Doce de Octubre and CNIO, Av. de Córdoba, s/n, 28041, Madrid, Spain. Electronic address: lpazaresr@seom.org. 12. West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, D-45147, Essen, Germany. Electronic address: Martin.Schuler@uk-essen.de. 13. Service de Pneumologie et Physiologie, CHU Grenoble-Alpes, 38700, La Tronche, France. Electronic address: dmoro-sibilot@chu-grenoble.fr. 14. Department of Medical Oncology, National Cancer Centre, 11 Hospital Drive, 169610, Singapore. Electronic address: dmoteh@nccs.com.sg. 15. Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, 961-8566, Niigata, Japan. Electronic address: htanaka@niigata-cc.jp. 16. Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan 2nd Rd, Yuexiu Qu, Guangzhou Shi, Guangdong Sheng, China. Electronic address: syylwu@live.cn. 17. Division of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, 7 Zhongshan South Road, Zhongzheng District, Taipei City, Taiwan. Electronic address: chihyang@ntu.edu.tw. 18. Sun Yat-Sen University Cancer Center, 651# DongFeng Road, East, 510060, China. Electronic address: Zhangli6@mail.sysu.edu.cn. 19. Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, 507 Zhengmin Road, Shanghai, China. Electronic address: caicunzhoudr@163.com. 20. Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216, Ingelheim am Rhein, Germany. Electronic address: angela.maerten@boehringer-ingelheim.com. 21. Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, 06877, USA. Electronic address: wenbo.tang@boehringer-ingelheim.com. 22. Internal Medicine III, Wakayama Medical University, 811-1 Kimiidera, Wakayama-shi, Wakayama-ken, 641-8509, Japan. Electronic address: nakagawa@med.kindai.ac.jp.
Abstract
OBJECTIVES: With the availability of several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), sequential therapy could potentially render EGFR mutation-positive non-small cell lung cancer a chronic disease in some patients. In this retrospective analysis of EGFR mutation-positive (Del19/L858R) patients receiving first-line afatinib in LUX-Lung 3, 6, and 7, we assessed uptake of, and outcomes following, subsequent therapies including the third-generation EGFR TKI, osimertinib. METHODS: Post-progression therapy data were prospectively collected during follow-up. Molecular testing of tumours at progression/discontinuation of afatinib was not mandatory. Duration of subsequent therapies, and survival following osimertinib, were calculated with Kaplan-Meier estimates. RESULTS: Among 553 patients who discontinued first-line afatinib, second-, third- and fourth-line therapy was administered in 394 (71%), 265 (48%), and 156 (28%) patients. The most common post-progression therapy was platinum-based chemotherapy (46%). Thirty-seven patients received subsequent osimertinib, 10 as second-line treatment. Median progression-free survival on afatinib in these 37 patients was 21.9 months. Median duration of osimertinib therapy was 20.2 months; median overall survival was not reached after a median follow-up of 4.7 years. CONCLUSIONS: Most patients treated with first-line afatinib received subsequent therapy. Although limited by sample size, enrichment, and a retrospective nature, data from patients who received sequential afatinib and osimertinib are encouraging, warranting further investigation.
OBJECTIVES: With the availability of several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), sequential therapy could potentially render EGFR mutation-positive non-small cell lung cancer a chronic disease in some patients. In this retrospective analysis of EGFR mutation-positive (Del19/L858R) patients receiving first-line afatinib in LUX-Lung 3, 6, and 7, we assessed uptake of, and outcomes following, subsequent therapies including the third-generation EGFR TKI, osimertinib. METHODS: Post-progression therapy data were prospectively collected during follow-up. Molecular testing of tumours at progression/discontinuation of afatinib was not mandatory. Duration of subsequent therapies, and survival following osimertinib, were calculated with Kaplan-Meier estimates. RESULTS: Among 553 patients who discontinued first-line afatinib, second-, third- and fourth-line therapy was administered in 394 (71%), 265 (48%), and 156 (28%) patients. The most common post-progression therapy was platinum-based chemotherapy (46%). Thirty-seven patients received subsequent osimertinib, 10 as second-line treatment. Median progression-free survival on afatinib in these 37 patients was 21.9 months. Median duration of osimertinib therapy was 20.2 months; median overall survival was not reached after a median follow-up of 4.7 years. CONCLUSIONS: Most patients treated with first-line afatinib received subsequent therapy. Although limited by sample size, enrichment, and a retrospective nature, data from patients who received sequential afatinib and osimertinib are encouraging, warranting further investigation.
Authors: Wang Chun Kwok; James Chung Man Ho; Terence Chi Chun Tam; Mary Sau Man Ip; David Chi Leung Lam Journal: Thorac Cancer Date: 2022-06-06 Impact factor: 3.223