Caicun Zhou1, Xingya Li2, Qiming Wang3, Guanghui Gao1, Yiping Zhang4, Jianhua Chen5, Yongqian Shu6, Yanping Hu7, Yun Fan4, Jian Fang8, Gongyan Chen9, Jun Zhao8, Jianxing He10, Fengying Wu1, Jianjun Zou11, Xiaoyu Zhu11, Xiang Lin11. 1. Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. 2. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 3. Henan Cancer Hospital, Zhengzhou, China. 4. Zhejiang Cancer Hospital, Hangzhou, China. 5. Cancer Hospital of Central South University, Changsha, China. 6. The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 7. Hubei Cancer Hospital, Wuhan, China. 8. Peking University Cancer Hospital and Institute, Beijing, China. 9. Harbin Medical University Cancer Hospital, Harbin, China. 10. The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 11. Jiangsu Hengrui Medicine Co, Ltd, Shanghai, China.
Abstract
PURPOSE: Targeted therapies against non-small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study. PATIENTS AND METHODS: Patients with stage IIIB or IV HER2-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC). RESULTS: Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different HER2 mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% v 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported. CONCLUSION: Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC.
PURPOSE: Targeted therapies against non-small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study. PATIENTS AND METHODS: Patients with stage IIIB or IV HER2-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC). RESULTS: Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different HER2 mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% v 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported. CONCLUSION:Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC.
Authors: Xiuning Le; Robin Cornelissen; Marina Garassino; Jeffrey M Clarke; Nishan Tchekmedyian; Jonathan W Goldman; Szu-Yun Leu; Gajanan Bhat; Francois Lebel; John V Heymach; Mark A Socinski Journal: J Clin Oncol Date: 2021-11-29 Impact factor: 44.544
Authors: Yasir Y Elamin; Jacqulyne P Robichaux; Brett W Carter; Mehmet Altan; Don L Gibbons; Frank V Fossella; Vincent K Lam; Anisha B Patel; Marcelo V Negrao; Xiuning Le; Frank E Mott; Jianjun Zhang; Lei Feng; George Blumenschein; Anne S Tsao; John V Heymach Journal: J Clin Oncol Date: 2021-09-22 Impact factor: 44.544
Authors: Bob T Li; Egbert F Smit; Yasushi Goto; Kazuhiko Nakagawa; Hibiki Udagawa; Julien Mazières; Misako Nagasaka; Lyudmila Bazhenova; Andreas N Saltos; Enriqueta Felip; Jose M Pacheco; Maurice Pérol; Luis Paz-Ares; Kapil Saxena; Ryota Shiga; Yingkai Cheng; Suddhasatta Acharyya; Patrik Vitazka; Javad Shahidi; David Planchard; Pasi A Jänne Journal: N Engl J Med Date: 2021-09-18 Impact factor: 176.079
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