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)

Ken Kato, Taroh Satoh, Kei Muro, Takaki Yoshikawa, Takao Tamura, Yasuo Hamamoto, Keisho Chin, Keiko Minashi, Masahiro Tsuda, Kensei Yamaguchi, Nozomu Machida, Taito Esaki, Masahiro Goto, Yoshito Komatsu, Takako Eguchi Nakajima, Naotoshi Sugimoto, Kazuhiro Yoshida, Eiji Oki, Tomohiro Nishina, Akihito Tsuji & 11 others Hirofumi Fujii, Kenji Kunieda, Soh Saitoh, Yasushi Omuro, Mizutomo Azuma, Yasuo Iwamoto, Keisei Taku, Sachio Fushida, Li Tzong Chen, Yoon Koo Kang, Narikazu Boku

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)344-354
Number of pages11
JournalGastric Cancer
Volume22
Issue number2
DOIs
Publication statusPublished - Mar 15 2019

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Esophageal Neoplasms
Stomach
Placebos
Drug Therapy
Survival
Disease-Free Survival
nivolumab
Population
Japan
Clinical Trials
Safety
ramucirumab

All Science Journal Classification (ASJC) codes

  • Oncology
  • Gastroenterology
  • Cancer Research

Cite this

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 journalArticle

Kato, K, Satoh, T, Muro, K, Yoshikawa, T, Tamura, T, Hamamoto, Y, Chin, K, Minashi, K, Tsuda, M, Yamaguchi, K, Machida, N, Esaki, T, Goto, M, Komatsu, Y, Nakajima, TE, Sugimoto, N, Yoshida, K, Oki, E, Nishina, T, Tsuji, A, Fujii, H, Kunieda, K, Saitoh, S, Omuro, Y, Azuma, M, Iwamoto, Y, Taku, K, Fushida, S, Chen, LT, Kang, YK & Boku, N 2019, '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)', Gastric Cancer, vol. 22, no. 2, pp. 344-354. https://doi.org/10.1007/s10120-018-0899-6
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. / 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). In: Gastric Cancer. 2019 ; Vol. 22, No. 2. pp. 344-354.
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title = "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)",
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.",
author = "Ken Kato and Taroh Satoh and Kei Muro and Takaki Yoshikawa and Takao Tamura and Yasuo Hamamoto and Keisho Chin and Keiko Minashi and Masahiro Tsuda and Kensei Yamaguchi and Nozomu Machida and Taito Esaki and Masahiro Goto and Yoshito Komatsu and Nakajima, {Takako Eguchi} and Naotoshi Sugimoto and Kazuhiro Yoshida and Eiji Oki and Tomohiro Nishina and Akihito Tsuji and Hirofumi Fujii and Kenji Kunieda and Soh Saitoh and Yasushi Omuro and Mizutomo Azuma and Yasuo Iwamoto and Keisei Taku and Sachio Fushida and Chen, {Li Tzong} and Kang, {Yoon Koo} and Narikazu Boku",
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month = "3",
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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

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.

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U2 - 10.1007/s10120-018-0899-6

DO - 10.1007/s10120-018-0899-6

M3 - Article

VL - 22

SP - 344

EP - 354

JO - Gastric Cancer

JF - Gastric Cancer

SN - 1436-3291

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