Abstract
Background: Nivolumab, an anti-programmed death-1 agent, showed survival benefits in Asian patients, including Japanese, with gastric/gastro-esophageal junction (G/GEJ) cancer. We report the analysis of the Japanese subpopulation from ATTRACTION-2 that evaluated nivolumab versus placebo in unresectable advanced or recurrent G/GEJ cancer after ≥ 2 chemotherapy regimens. Methods: Data from the Japanese subpopulation in the randomized, double-blind, placebo-controlled, phase 3 trial were analyzed (data cutoff, February 25, 2017). Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). Results: Among the overall study population of 493 patients, 226 (nivolumab 152; placebo 74) were enrolled from 28 sites in Japan. In the Japanese subset, median OS was longer with nivolumab versus placebo (5.4 months, 95% CI 4.6–7.4 versus 3.6 months, 95% CI 2.8–5.0). The risk of death was lower in the nivolumab versus placebo group (hazard ratio 0.58, 95% CI 0.42–0.78; p = 0.0002). Incidences of serious adverse events were 23% (35/152) and 25% (18/72) in the nivolumab and placebo groups, respectively. In the Japanese ITT population, 22% of nivolumab-treated and 28% of placebo-treated patients received prior ramucirumab treatment. Overall, clinical activity of nivolumab was observed regardless of prior ramucirumab use. In the nivolumab group, ORR and PFS were numerically higher in patients with prior ramucirumab use than in those without. Conclusions: In the Japanese subpopulation, patients receiving nivolumab had longer OS, similar to the overall population, with a manageable safety profile. The interaction between nivolumab and ramucirumab will be clarified in ongoing clinical trials.
| Original language | English |
|---|---|
| Pages (from-to) | 344-354 |
| Number of pages | 11 |
| Journal | Gastric Cancer |
| Volume | 22 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2019 Mar 15 |
Keywords
- Gastric cancer
- Gastro-esophageal junction cancer
- Japan
- Nivolumab
ASJC Scopus subject areas
- Oncology
- Gastroenterology
- Cancer Research
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A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2). / Kato, Ken; Satoh, Taroh; Muro, Kei; Yoshikawa, Takaki; Tamura, Takao; Hamamoto, Yasuo; Chin, Keisho; Minashi, Keiko; Tsuda, Masahiro; Yamaguchi, Kensei; Machida, Nozomu; Esaki, Taito; Goto, Masahiro; Komatsu, Yoshito; Nakajima, Takako Eguchi; Sugimoto, Naotoshi; Yoshida, Kazuhiro; Oki, Eiji; Nishina, Tomohiro; Tsuji, Akihito; Fujii, Hirofumi; Kunieda, Kenji; Saitoh, Soh; Omuro, Yasushi; Azuma, Mizutomo; Iwamoto, Yasuo; Taku, Keisei; Fushida, Sachio; Chen, Li Tzong; Kang, Yoon Koo; Boku, Narikazu.
In: Gastric Cancer, Vol. 22, No. 2, 15.03.2019, p. 344-354.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2)
AU - Kato, Ken
AU - Satoh, Taroh
AU - Muro, Kei
AU - Yoshikawa, Takaki
AU - Tamura, Takao
AU - Hamamoto, Yasuo
AU - Chin, Keisho
AU - Minashi, Keiko
AU - Tsuda, Masahiro
AU - Yamaguchi, Kensei
AU - Machida, Nozomu
AU - Esaki, Taito
AU - Goto, Masahiro
AU - Komatsu, Yoshito
AU - Nakajima, Takako Eguchi
AU - Sugimoto, Naotoshi
AU - Yoshida, Kazuhiro
AU - Oki, Eiji
AU - Nishina, Tomohiro
AU - Tsuji, Akihito
AU - Fujii, Hirofumi
AU - Kunieda, Kenji
AU - Saitoh, Soh
AU - Omuro, Yasushi
AU - Azuma, Mizutomo
AU - Iwamoto, Yasuo
AU - Taku, Keisei
AU - Fushida, Sachio
AU - Chen, Li Tzong
AU - Kang, Yoon Koo
AU - Boku, Narikazu
N1 - Funding Information: Acknowledgements We thank the patients, their families, and the investigators. Editorial support, in the form of medical writing, assembling tables and creating high-resolution images based on authors’ detailed directions, collating author comments, copyediting, fact checking, and referencing, was provided by Annirudha Chillar, MD, PhD, of Cactus Communications, and funded by Ono Pharmaceutical Co., Ltd., Osaka, Japan, and Bristol-Myers Squibb, Princeton, NJ, USA. Funding Information: Funding This study was funded by Ono Pharmaceutical Co., Ltd., Osaka, Japan, and Bristol-Myers Squibb, Princeton, NJ, USA. Funding Information: Conflict of interest Ken Kato received research funds from Ono Pharmaceutical, MSD, Shionogi, and Merck Serono for this study, and research funds from Merck, Shionogi, and Ono Pharmaceutical for activities outside the submitted work. Taroh Satoh received research grants and honoraria from Ono Pharmaceutical and Bristol-Myers Squibb and a department donated by Ono Pharmaceutical for this study; research grants and honoraria from Yakult Honsha, Chugai Pharmaceutical, Eli Lilly, Merck Serono, Takeda Pharmaceutical, Taiho Pharmaceutical, and MSD; and a department donated by Yakult Honsha and Chugai Pharmaceutical for activities outside the submitted work. Kei Muro received a grant from Ono Pharmaceutical for this study; grants from Ono Pharmaceutical, MSD, Daiichi Sankyo, Kyowa Hakko Kirin, Shionogi, and Gilead Sciences for activities outside the submitted work; and personal fees from Chugai Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, Merck Serono, Eli Lilly, and Yakult Honsha. Takaki Yoshikawa received grants from Ono Pharmaceutical and Bristol-Myers Squibb for this study; grants and honoraria from Chugai Pharmaceutical and Taiho Pharmaceutical; grants and advisory fees from Novartis, Ono Pharmaceutical, Eli Lilly Japan, Johnson & Johnson, and Covidien; and honoraria from Abbott Japan, Kaken, Yakult Honsha, Nippon Kayaku, Takeda Pharmaceutical, and Olympus for activities outside the submitted work. Takao Tamura received grants from Ono Pharmaceutical and Bristol-Myers Squibb for this study, and grants from MSD Pharmaceutical, Merck, and Daiichi Sankyo for activities outside the submitted work. Keiko Minashi received research funding from Ono Pharmaceutical for this study. Kensei Yamaguchi received grants from Ono Pharmaceutical and Bristol-Myers Squibb for this study. Nozomu Machida received a grant from Ono Pharmaceutical for this study, and grants from Taiho Pharmaceutical, MSD, and Eli Lilly for activities outside the submitted work. Taito Esaki received a grant from Ono Pharmaceutical for this study; grants from Dainippon Sumitomo, Novartis, MSD, Daiichi Sankyo, Pfizer, Boehringer Ingelheim, Ono Pharmaceutical, Bayer, Astellas, Showa, AstraZeneca, and GSK; personal fees from Eisai, Ky-owa Hakko Kirin, Chugai Pharmaceutical, and Bristol-Myers Squibb; and grants and personal fees from Taiho Pharmaceutical, Merck Se-rono, Eli Lilly, Nippon Kayaku, and Takeda Pharmaceutical for activities outside the submitted work. Masahiro Goto received a grant, personal fees, and non-financial support from Ono Pharmaceutical for this study; grants, personal fees, and non-financial support from Taiho Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Kyowa Hakko Kirin, and Mochida Pharmaceutical; and personal fees and nonfinancial support from Takeda Pharmaceutical, Novartis, and Bayer Yakuhin for activities outside the submitted work. Yoshito Komatsu received a grant from Ono Pharmaceutical for this study; lecturer’s fee and research expenses from Ono Pharmaceutical, MSD, Eli Lilly, Merck, AstraZeneca, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, NCC, Kyowa Hakko Kirin, Takeda Pharmaceutical, Sanofi, Yakult Honsha, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer, Pfizer, and Novartis; and research expenses from Linical and TCOG for activities outside the submitted work. Takako Eguchi Naka-jima received a grant from Ono Pharmaceutical for this study; grants and personal fees from Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Takeda Pharmaceutical, Merck Serono, Ono Pharmaceutical, and Dainippon Sumitomo; grants from Yakult Honsha, Eisai, Sanofi, Amgen Astellas BioPharma, and AstraZeneca; and personal fees from Sawai Pharmaceutical, Kyowa Hakko Kirin, Bristol-Myers Squibb, Bayer Yakuhin, and Maruho for activities outside the submitted work. Naotoshi Sugimoto received a grant from Ono Pharmaceutical for this study, and grants from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, MSD, Daiichi Sankyo, and Dainippon Sumitomo for activities outside the submitted work. Kazuhiro Yoshida received grants, personal fees, and non-financial support from Ono Pharmaceutical for this study; grants, personal fees, and non-financial support from Taiho Pharmaceutical, Chugai Pharmaceutical, Yakult Honsha, Eli Lilly Japan, Daiichi Sankyo, Merck Serono, Novartis Pharma, EA Pharma, Takeda Pharmaceutical, and Sanofi; grants and personal fees from Johnson & Johnson and Covidien Japan; grants from Nippon Kayaku, Otsuka Pharmaceutical, and Dainippon Sumitomo; and personal fees from MSD K.K. and Bayer Yakuhin for activities outside the submitted work. Eiji Oki received a grant from Ono Pharmaceutical for this study, and honoraria for lecturing from Ono Pharmaceutical, Taiho Pharmaceutical, Yakult Honsha, Merck Serono, Takeda Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, and Bristol-Myers Squibb. Aki-hito Tsuji received a grant from Ono Pharmaceutical for this study, and honoraria from Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, Merck Serono, Takeda Pharmaceutical, and Bristol-Myers Squibb Japan for activities outside the submitted work. Mizutomo Azuma received a grant and personal fees from Ono Pharmaceutical for this study. Keisei Taku, Masahiro Tsuda, Tomohiro Nishina, Hiro-fumi Fujii, Kenji Kunieda, Soh Saito, Yasushi Omuro, Yasuo Iwamoto, Sachio Fushida, Yasuo Hamamoto, and Keisho Chin received grants from Ono Pharmaceutical for this study. Li-Tzong Chen received a grant from Ono Pharmaceutical for this study; grants, personal fees, and non-financial support from Novartis, TTY, and Syncore; grants from the Ministry of Science and Technology (Taiwan), Ministry of Health and Welfare (Taiwan), Pfizer, GSK, Merck Serono, OBI, and Polaris; grants and non-financial support from Celgene; and personal fees from Eli Lilly, PharmaEngine, Shire, MSD, Bristol-Myers Squibb, Ono Pharmaceutical, Five Prime, and Merrimack for activities outside the submitted work. Yoon-Koo Kang received a grant from Ono Pharmaceutical for this study, and personal fees from Ono Pharmaceutical, Bristol-Myers Squibb, Daehwa, and Blueprint for activities outside the submitted work. Narikazu Boku received a grant and personal fees from Ono Pharmaceutical for this study, and personal fees from Chugai Pharmaceutical, Merck Serono, and AstraZeneca for activities outside the submitted work. Publisher Copyright: © 2018, The Author(s).
PY - 2019/3/15
Y1 - 2019/3/15
N2 - Background: Nivolumab, an anti-programmed death-1 agent, showed survival benefits in Asian patients, including Japanese, with gastric/gastro-esophageal junction (G/GEJ) cancer. We report the analysis of the Japanese subpopulation from ATTRACTION-2 that evaluated nivolumab versus placebo in unresectable advanced or recurrent G/GEJ cancer after ≥ 2 chemotherapy regimens. Methods: Data from the Japanese subpopulation in the randomized, double-blind, placebo-controlled, phase 3 trial were analyzed (data cutoff, February 25, 2017). Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). Results: Among the overall study population of 493 patients, 226 (nivolumab 152; placebo 74) were enrolled from 28 sites in Japan. In the Japanese subset, median OS was longer with nivolumab versus placebo (5.4 months, 95% CI 4.6–7.4 versus 3.6 months, 95% CI 2.8–5.0). The risk of death was lower in the nivolumab versus placebo group (hazard ratio 0.58, 95% CI 0.42–0.78; p = 0.0002). Incidences of serious adverse events were 23% (35/152) and 25% (18/72) in the nivolumab and placebo groups, respectively. In the Japanese ITT population, 22% of nivolumab-treated and 28% of placebo-treated patients received prior ramucirumab treatment. Overall, clinical activity of nivolumab was observed regardless of prior ramucirumab use. In the nivolumab group, ORR and PFS were numerically higher in patients with prior ramucirumab use than in those without. Conclusions: In the Japanese subpopulation, patients receiving nivolumab had longer OS, similar to the overall population, with a manageable safety profile. The interaction between nivolumab and ramucirumab will be clarified in ongoing clinical trials.
AB - Background: Nivolumab, an anti-programmed death-1 agent, showed survival benefits in Asian patients, including Japanese, with gastric/gastro-esophageal junction (G/GEJ) cancer. We report the analysis of the Japanese subpopulation from ATTRACTION-2 that evaluated nivolumab versus placebo in unresectable advanced or recurrent G/GEJ cancer after ≥ 2 chemotherapy regimens. Methods: Data from the Japanese subpopulation in the randomized, double-blind, placebo-controlled, phase 3 trial were analyzed (data cutoff, February 25, 2017). Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). Results: Among the overall study population of 493 patients, 226 (nivolumab 152; placebo 74) were enrolled from 28 sites in Japan. In the Japanese subset, median OS was longer with nivolumab versus placebo (5.4 months, 95% CI 4.6–7.4 versus 3.6 months, 95% CI 2.8–5.0). The risk of death was lower in the nivolumab versus placebo group (hazard ratio 0.58, 95% CI 0.42–0.78; p = 0.0002). Incidences of serious adverse events were 23% (35/152) and 25% (18/72) in the nivolumab and placebo groups, respectively. In the Japanese ITT population, 22% of nivolumab-treated and 28% of placebo-treated patients received prior ramucirumab treatment. Overall, clinical activity of nivolumab was observed regardless of prior ramucirumab use. In the nivolumab group, ORR and PFS were numerically higher in patients with prior ramucirumab use than in those without. Conclusions: In the Japanese subpopulation, patients receiving nivolumab had longer OS, similar to the overall population, with a manageable safety profile. The interaction between nivolumab and ramucirumab will be clarified in ongoing clinical trials.
KW - Gastric cancer
KW - Gastro-esophageal junction cancer
KW - Japan
KW - Nivolumab
UR - http://www.scopus.com/inward/record.url?scp=85057801395&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85057801395&partnerID=8YFLogxK
U2 - 10.1007/s10120-018-0899-6
DO - 10.1007/s10120-018-0899-6
M3 - Article
C2 - 30506519
AN - SCOPUS:85057801395
VL - 22
SP - 344
EP - 354
JO - Gastric Cancer
JF - Gastric Cancer
SN - 1436-3291
IS - 2
ER -