Background: This multicenter, randomized phase II trial was conducted to compare the efficacy and safety of nimotuzumab plus irinotecan (N-IRI) versus irinotecan alone (IRI) in patients with advanced gastric cancer (AGC) showing disease progression after previous 5-fluorouracil-based therapy. Methods: Irinotecan-naive patients (n = 82) received N-IRI (nimotuzumab 400 mg weekly plus irinotecan 150 mg/m2 biweekly) or IRI (irinotecan 150 mg/m2 biweekly) until disease progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), response rate (RR), safety, tolerability, and the correlation between efficacy and tumor epidermal growth factor receptor (EGFR) expression. Results: Of 83 patients, 40 and 43 patients were randomly assigned to the N-IRI and IRI groups, respectively. In the N-IRI/IRI treatment group, median PFS was 73.0/85.0 days (P = 0.5668), and median OS and RR at 18 months were 250.5/232.0 days (P = 0.9778) and 18.4/10.3 %, respectively. Median PFS and OS in the EGFR 2+/3+ subgroups were 118.5/59.0 and 358.5/229.5 days, respectively. The RR was 33.3/0.0 % in the N-IRI/IRI treatment group. The incidence of grade 3 or higher adverse events was 77.5/64.3 %. No adverse events of grade 3 or higher skin rash or grade 3 or higher infusion-related reaction were reported. Conclusions: There was no superiority of N-IRI over IRI alone in terms of PFS in 5-fluorouracil-refractory AGC patients. However, N-IRI showed potential improvement in the EGFR 2+/3+ subgroup based on improved RR, PFS, and OS.
Bibliographical noteFunding Information:
We thank all the patients, their families, and the institutions involved in this study. The authors also thank the following individual board members for their contributions to this report: Independent Data Monitoring Committee, Keiichi Nagao, Noriyuki Masuda, Ichinosuke Hyodo, Baek-Yeol Ryoo, Young Iee Park, and Hong Suk Song; Efficacy Evaluation Committee, Atsushi Sato, Junji Tanaka, and Dae Young Zang; and Medical Advisors, Yutaka Ariyoshi and Kiyohiko Hatake. This trial was supported by a grant from Daiichi Sankyo Co., Ltd., Japan, and Kuhnil Pharm. Co., Ltd., Republic of Korea.
T. Satoh, Y. Komatsu, Y. Yamada, and M. Munakata received research funding and honoraria from Daiichi Sankyo. Y.H. Kim received research funding and an honorarium from Kuhnil Pharm. K. Yamaguchi, N. Fuse, T. Ura, and S. Saitoh received research funding from Daiichi Sankyo. H. Yasui and S. Morita received honoraria from Daiichi Sankyo. Y. Sasaki, K. Nishio, and Y. Sakata received research funding, honoraria, and expert testimony from Daiichi Sankyo. K.H. Lee, S.Y. Rha, S.H. Park, T.Y. Kim, and S.Y. Kim have no conflicts of interests to declare.
© 2014, The Author(s).
All Science Journal Classification (ASJC) codes
- Cancer Research