Miyako Satouchi1, Yoshikazu Kotani, Taro Shibata, Masahiko Ando, Kazuhiko Nakagawa, Nobuyuki Yamamoto, Yukito Ichinose, Yuichiro Ohe, Makoto Nishio, Toyoaki Hida, Koji Takeda, Tatsuo Kimura, Koichi Minato, Akira Yokoyama, Shinji Atagi, Haruhiko Fukuda, Tomohide Tamura, Nagahiro Saijo. 1. Miyako Satouchi, Hyogo Cancer Center, Akashi; Yoshikazu Kotani, Kobe University Graduate School of Medicine, Kobe; Taro Shibata and Haruhiko Fukuda, Japan Clinical Oncology Group Data Center, Multi-Institutional Clinical Trial Support Center, National Cancer Center; Yuichiro Ohe, National Cancer Center Hospital East; Makoto Nishio, Cancer Institute Hospital, Japanese Foundation For Cancer Research; Tomohide Tamura, National Cancer Center Hospital; Nagahiro Saijo, Japanese Society of Medical Oncology, Tokyo; Masahiko Ando, Kyoto University School of Public Health, Kyoto; Kazuhiko Nakagawa, Kinki University School of Medicine; Koji Takeda, Osaka City General Hospital; Tatsuo Kimura, Graduate School of Medicine, Osaka City University; Shinji Atagi, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka; Nobuyuki Yamamoto, Shizuoka Cancer Center, Shizuoka; Yukito Ichinose, National Hospital Organization Kyushu Cancer Center, Fukuoka; Toyoaki Hida, Aichi Cancer Center, Nagoya; Koichi Minato, Gunma Cancer Center, Gunma; and Akira Yokoyama, Niigata Cancer Center Hospital, Niigata, Japan.
Abstract
PURPOSE: This randomized phase III trial was conducted to confirm noninferiority of amrubicin plus cisplatin (AP) compared with irinotecan plus cisplatin (IP) in terms of overall survival (OS) in chemotherapy-naive patients with extensive-disease (ED) small-cell lung cancer (SCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with ED-SCLC were randomly assigned to receive IP, composed of irinotecan 60 mg/m(2) on days 1, 8, and 15 and cisplatin 60 mg/m(2) on day 1 every 4 weeks, or AP, composed of amrubicin 40 mg/m(2) on days 1, 2, and 3 and cisplatin 60 mg/m(2) on day 1 every 3 weeks. RESULTS: A total of 284 patients were randomly assigned to IP (n = 142) and AP (n = 142) arms. The point estimate of OS hazard ratio (HR) for AP to IP in the second interim analysis exceeded the noninferior margin (HR, 1.31), resulting in early publication because of futility. In updated analysis, median survival time was 17.7 (IP) versus 15.0 months (AP; HR, 1.43; 95% CI, 1.10 to 1.85), median progression-free survival was 5.6 (IP) versus 5.1 months (AP; HR, 1.42; 95% CI, 1.16 to 1.73), and response rate was 72.3% (IP) versus 77.9% (AP; P = .33). Adverse events observed in IP and AP arms were grade 4 neutropenia (22.5% v 79.3%), grade 3 to 4 febrile neutropenia (10.6% v 32.1%), and grade 3 to 4 diarrhea (7.7% v 1.4%). CONCLUSION: AP proved inferior to IP in this trial, perhaps because the efficacy of amrubicin as a salvage therapy was differentially beneficial to IP. IP remains the standard treatment for extensive-stage SCLC in Japan.
RCT Entities:
PURPOSE: This randomized phase III trial was conducted to confirm noninferiority of amrubicin plus cisplatin (AP) compared with irinotecan plus cisplatin (IP) in terms of overall survival (OS) in chemotherapy-naive patients with extensive-disease (ED) small-cell lung cancer (SCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with ED-SCLC were randomly assigned to receive IP, composed of irinotecan 60 mg/m(2) on days 1, 8, and 15 and cisplatin 60 mg/m(2) on day 1 every 4 weeks, or AP, composed of amrubicin 40 mg/m(2) on days 1, 2, and 3 and cisplatin 60 mg/m(2) on day 1 every 3 weeks. RESULTS: A total of 284 patients were randomly assigned to IP (n = 142) and AP (n = 142) arms. The point estimate of OS hazard ratio (HR) for AP to IP in the second interim analysis exceeded the noninferior margin (HR, 1.31), resulting in early publication because of futility. In updated analysis, median survival time was 17.7 (IP) versus 15.0 months (AP; HR, 1.43; 95% CI, 1.10 to 1.85), median progression-free survival was 5.6 (IP) versus 5.1 months (AP; HR, 1.42; 95% CI, 1.16 to 1.73), and response rate was 72.3% (IP) versus 77.9% (AP; P = .33). Adverse events observed in IP and AP arms were grade 4 neutropenia (22.5% v 79.3%), grade 3 to 4 febrile neutropenia (10.6% v 32.1%), and grade 3 to 4 diarrhea (7.7% v 1.4%). CONCLUSION: AP proved inferior to IP in this trial, perhaps because the efficacy of amrubicin as a salvage therapy was differentially beneficial to IP. IP remains the standard treatment for extensive-stage SCLC in Japan.