Y K Shi1, L Wang2, B H Han3, W Li4, P Yu5, Y P Liu6, C M Ding7, X Song8, Z Y Ma9, X L Ren10, J F Feng11, H L Zhang12, G Y Chen13, X H Han2, N Wu14, C Yao15, Y Song16, S C Zhang17, W Song18, X Q Liu19, S J Zhao14, Y C Lin20, X Q Ye21, K Li22, Y Q Shu23, L M Ding24, F L Tan24, Y Sun2. 1. Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing. Electronic address: syuankai@cicams.ac.cn. 2. Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing. 3. Department of Pulmonology, Shanghai Chest Hospital, Shanghai. 4. Department of Oncology, The First Hospital Affiliated to Jilin University, Changchun. 5. Department of Lung Cancer Medical Oncology, Sichuan Cancer Hospital, Chengdu. 6. Department of Medical Oncology, The First Hospital of China Medical University, Shenyang. 7. Department of Respiratory Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang. 8. Department of Respiratory Medicine, Shanxi Provincial Tumor Hospital, Taiyuan. 9. Department of Oncology, Henan Cancer Hospital, Zhengzhou. 10. Department of Respiratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an. 11. Department of Oncology, Jiangsu Cancer Hospital, Nanjing. 12. Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an. 13. Department of Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin. 14. Department of Imaging Diagnosis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing. 15. Department of Biostatistics, Peking University Clinical Research Institute, Beijing. 16. Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing. 17. Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing. 18. Department of Radiology, Peking Union Medical College Hospital, Beijing. 19. Department of Pulmonary Oncology, The 307th Hospital of Chinese People's Liberation Army, Beijing. 20. Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou. 21. Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang. 22. Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin. 23. Department of Oncology, Jiangsu Provincial Hospital, Nanjing. 24. Betta Pharmaceuticals Co., Ltd, Hangzhou, China.
Abstract
BACKGROUND: Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. PATIENTS AND METHODS: Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety. RESULTS: Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group. CONCLUSIONS: First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.
BACKGROUND: Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. PATIENTS AND METHODS: Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety. RESULTS: Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group. CONCLUSIONS: First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.
Authors: Xiaohong Han; Rongrong Luo; Lin Wang; Lei Zhang; Tao Wang; Yan Zhao; Shanshan Xiao; Nan Qiao; Chi Xu; Lieming Ding; Zhishang Zhang; Yuankai Shi Journal: Am J Cancer Res Date: 2020-12-01 Impact factor: 6.166
Authors: Asunción Díaz-Serrano; Pablo Gella; Elisabeth Jiménez; Jon Zugazagoitia; Luis Paz-Ares Rodríguez Journal: Drugs Date: 2018-06 Impact factor: 9.546