Clinical Trial

. 2020 May;23(3):510-519.

doi: 10.1007/s10120-019-01034-7. Epub 2019 Dec 20.

A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data

Li-Tzong Chen^{1

2}, Taroh Satoh³, Min-Hee Ryu⁴, Yee Chao⁵, Ken Kato⁶, Hyun Cheol Chung⁷, Jen-Shi Chen⁸, Kei Muro⁹, Won Ki Kang¹⁰, Kun-Huei Yeh^{11

12}, Takaki Yoshikawa^{13

14}, Sang Cheul Oh¹⁵, Li-Yuan Bai¹⁶, Takao Tamura^{17

18}, Keun-Wook Lee¹⁹, Yasuo Hamamoto²⁰, Jong Gwang Kim²¹, Keisho Chin²², Do-Youn Oh²³, Keiko Minashi²⁴, Jae Yong Cho²⁵, Masahiro Tsuda²⁶, Hiroki Sameshima²⁷, Yoon-Koo Kang⁴, Narikazu Boku²⁸

Affiliations

¹ National Institute of Cancer Research, National Health Research Institutes, National Cheng Kung University, Tainan, Taiwan.
² Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
³ Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan.
⁴ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁵ Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁶ Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
⁷ Division of Medical Oncology, Yonsei Cancer Center, Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.
⁸ Division of Hematology and Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
⁹ Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
¹⁰ Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
¹¹ National Taiwan University Cancer Center, Taipei, Taiwan.
¹² Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
¹³ Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan.
¹⁴ Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan.
¹⁵ Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, South Korea.
¹⁶ Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
¹⁷ Department of Medical Oncology, Faculty of Medicine, Kindai University, Osakasayama, Japan.
¹⁸ Department of Medical Oncology, Kindai University Nara Hospital, Ikoma, Japan.
¹⁹ Division of Hematology and Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
²⁰ Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan.
²¹ Kyungpook National University School of Medicine, Daegu, South Korea.
²² Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
²³ Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
²⁴ Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan.
²⁵ Department of Medical Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
²⁶ Department of Gastroenterological Oncology, Hyogo Cancer Center, Akashi, Japan.
²⁷ Medical Oncology, Medical Affairs, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
²⁸ Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. nboku@ncc.go.jp.

PMID: 31863227
PMCID: PMC7165140
DOI: 10.1007/s10120-019-01034-7

Clinical Trial

A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data

Li-Tzong Chen et al. Gastric Cancer. 2020 May.

. 2020 May;23(3):510-519.

doi: 10.1007/s10120-019-01034-7. Epub 2019 Dec 20.

Authors

Affiliations

¹ National Institute of Cancer Research, National Health Research Institutes, National Cheng Kung University, Tainan, Taiwan.
² Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
³ Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan.
⁴ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁵ Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁶ Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
⁷ Division of Medical Oncology, Yonsei Cancer Center, Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.
⁸ Division of Hematology and Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
⁹ Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
¹⁰ Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
¹¹ National Taiwan University Cancer Center, Taipei, Taiwan.
¹² Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
¹³ Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan.
¹⁴ Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan.
¹⁵ Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, South Korea.
¹⁶ Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
¹⁷ Department of Medical Oncology, Faculty of Medicine, Kindai University, Osakasayama, Japan.
¹⁸ Department of Medical Oncology, Kindai University Nara Hospital, Ikoma, Japan.
¹⁹ Division of Hematology and Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
²⁰ Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan.
²¹ Kyungpook National University School of Medicine, Daegu, South Korea.
²² Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
²³ Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
²⁴ Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan.
²⁵ Department of Medical Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
²⁶ Department of Gastroenterological Oncology, Hyogo Cancer Center, Akashi, Japan.
²⁷ Medical Oncology, Medical Affairs, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
²⁸ Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. nboku@ncc.go.jp.

PMID: 31863227
PMCID: PMC7165140
DOI: 10.1007/s10120-019-01034-7

Abstract

Background: Nivolumab showed improvement in overall survival (OS) in ATTRACTION-2, the first phase 3 study in patients with gastric/gastroesophageal junction (G/GEJ) cancer treated with ≥ 2 chemotherapy regimens. The 2-year follow-up results of ATTRACTION-2 are presented herein.

Methods: ATTRACTION-2 was a randomized, double-blind, placebo-controlled, phase 3 trial (49 sites; Japan, South Korea, and Taiwan). The median (min-max) follow-up period was 27.3 (24.1-36.3) months. The primary endpoint was OS. A subanalysis of OS was performed based on best overall response and tumor-programmed death ligand-1 (PD-L1) expression status.

Results: Overall, 493 of 601 screened patients were randomized (2:1) to receive nivolumab (330) or placebo (163). OS (median [95% confidence interval; CI]) was significantly longer in the nivolumab group (5.26 [4.60-6.37] vs 4.14 [3.42-4.86] months in placebo group) at the 2-year follow-up (hazard ratio [95% CI], 0.62 [0.51-0.76]; P < 0.0001). A higher OS rate was observed in the nivolumab vs placebo group at 1 (27.3% vs 11.6%) and 2 years (10.6% vs 3.2%). The OS benefit was observed regardless of tumor PD-L1 expression. Among patients with a complete or partial response (CR or PR) in the nivolumab group, the median OS (95% CI) was 26.6 (21.65-not applicable) months; the OS rates at 1 and 2 years were 87.1% and 61.3%, respectively. No new safety signals were identified.

Conclusions: Nivolumab treatment resulted in clinically meaningful long-term improvements in OS in patients with previously treated G/GEJ cancer. The long-term survival benefit of nivolumab was most evident in patients with a CR or PR.

Keywords: Gastric cancer; Gastroesophageal junction cancer; Long-term; Nivolumab; Placebo.

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Conflict of interest statement

L-TC reports personal fees from Ono Pharmaceutical Co., Ltd.,; grants and personal fees from Bristol-Myers Squibb for the work under consideration for publication; grants from the Ministry of Science and Technology (Taiwan), Ministry of Health and Welfare (Taiwan), Pfizer (study funding), OBI (preclinical testing), and Polaris (translational research funding); personal fees from AstraZeneca (honorarium), Eli Lilly (honorarium), Five Prime (honorarium), Ipsen, Shire (honorarium), Ono Pharmaceutical Co., Ltd. (honorarium), and MSD (honorarium); personal fees and non-financial support from PharmaEngine (honorarium and study medication); grants, personal fees, and non-financial support (study medication, funding support, and honorarium) from Novartis, Syncore, and TTY; grants and personal fees (honorarium and translation funding) from Bristol-Myers Squibb; and grants and non-financial support (study medication and funding) from Celgene, outside the submitted work. Dr. Satoh reports grants and personal fees from ONO pharmaceutical CO.,LTD., grants and personal fees from Bristol-Myers-Squib, during the conduct of the study; grants and personal fees from Yakult Honsha, grants and personal fees from Chugai-Pharmaceutical, grants and personal fees from Elli-Lilly, grants and personal fees from Merck-Serono, grants and personal fees from Takeda Pharmaceutical, grants and personal fees from Taiho Pharmaceutical, grants and personal fees from MSD, outside the submitted work. M-HR reports honorarium and advisory board fees from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb, MSD, Eli Lilly, Taiho Pharmaceutical, Novartis, and Daehwa Pharmaceutical, outside the submitted work. YC, WKK, S-CO, L-YB, YH, JGK, KC, and JYC report grants from Ono Pharmaceutical Co., Ltd., for the work under consideration for publication. KK reports research funding from Ono Pharmaceutical Co., Ltd., for the work under consideration for publication, and research funding from Merck & Co., Shionogi & Co., Ltd., Ono Pharmaceutical Co., Ltd., MSD, Merck Serono, and BeiGene, outside the submitted work. HCC reports grants from Ono Pharmaceutical Co., Ltd., for the work under consideration for publication; grants (research support) from Eli Lilly, GlaxoSmithKline, MSD, Merck Serono, Bristol-Myers Squibb, Ono Pharmaceutical Co., Ltd., and Taiho Pharmaceutical; personal fees (honoraria) from Merck Serono, Eli Lilly, Foundation Medicine, and Roche; and personal fees (consultation) from Taiho Pharmaceutical, Celltrion, MSD, Eli Lilly, Quintiles, Bristol-Myers Squibb, and Merck Serono, outside the submitted work. J-SC reports grants and personal fees (consultation) from Ono Pharmaceutical Co., Ltd., for the work under consideration for publication. KM reports grants from Ono Pharmaceutical Co., Ltd., for the work under consideration for publication; grants and personal fees from Ono Pharmaceutical Co., Ltd., and Sanofi; grants from MSD, Daiichi Sankyo, Parexel International, Shionogi Pharmaceutical, Sumitomo Dainippon Pharma, Pfizer, Mediscience Planning, Solasia Pharma, and Merck Serono; and personal fees from Eli Lilly, Chugai Pharmaceutical, Takeda Pharmaceutical, Taiho Pharmaceutical, Bristol-Myers Squibb, and Bayer, outside the submitted work. K-HY reports personal fees from Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb, for the work under consideration for publication, and personal fees (honoraria) from Boehringer Ingelheim, Takeda Pharmaceutical, MSD, Eli Lilly, and Amgen, outside the submitted work. TY reports grants from Ono Pharmaceutical Co., Ltd., and Bristol-Myers Squibb for the work under consideration for publication; grants and personal fees (honoraria) from Chugai and Taiho Pharmaceutical; personal fees (honoraria) from Bristol-Myers Squibb, Yakult, Nihon Kayaku, Olympus, Daiichi Sankyo, MSD, and Terumo; and personal fees (honoraria and advisory role) from Ono Pharmaceutical Co., Ltd., Eli Lilly (Japan), Johnson and Johnson, and Covidien, outside the submitted work. TT reports grants from Ono Pharmaceutical Co., Ltd., and Bristol-Myers Squibb for the work under consideration for publication; grants from MDS Pharmaceutical, Merck Serono Co., Ltd., and Chugai Pharmaceutical Co, Ltd.; and grants and personal fees from Daiichi Sankyo Ltd., Takeda Pharmaceutical, and Taiho Pharmaceutical, outside the submitted work. K-WL reports grants from Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., AstraZeneca/MedImmune, Merck KGaA, Pfizer, Macrogenics, Green Cross Corp, Five Prime Therapeutics, Pharmacyclics, LSK BioPharma, ALX Oncology, Zymeworks, BeiGene, Genexine, ASLAN Pharmaceuticals, and Array BioPharma to his institution for conducting clinical trials, and personal fees (honoraria) from Bristol-Myers Squibb, Eli Lilly, and Genexine, outside the submitted work. D-YO reports grants from AstraZeneca outside the submitted work. KM reports research funding from Ono Pharmaceutical Co., Ltd., for the work under consideration for publication. MT reports grants from Ono Pharmaceutical Co., Ltd., outside the submitted work. HS reports personal fees and employment with Ono Pharmaceutical Co., Ltd., outside the submitted work. Y-KK reports grants from Ono Pharmaceutical Co., Ltd., for the work under consideration for publication, and personal fees from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Daehwa Pharmaceutical, Blueprint, Merck, and Astellas, outside the submitted work. NB reports grants and personal fees from Ono Pharmaceutical Co., Ltd., and personal fees from Bristol-Myers Squibb for the work under consideration for publication; grants and personal fees from Taiho Pharmaceutical and personal fees from Chugai and Eli Lilly, outside the submitted work.

Figures

**Fig. 1**
Kaplan–Meier plot of OS (a) and PFS (b) after 2 years of follow-up. Marks on the curve indicate patients who were censored. CI confidence interval, HR hazard ratio, OS overall survival, *PFS* progression-free survival

**Fig. 2**
Subanalysis of OS by BOR among patients with CR + PR (a), SD (b), and PD (c). Marks on the curve indicate patients who were censored. *BOR* best overall response, CI confidence interval, CR complete response, HR hazard ratio, NA not applicable, OS overall survival, PD progressive disease, PR partial response, SD stable disease

**Fig. 3**
Emergence of treatment-related AEs (any grade) of special interest over time. AE adverse event

See this image and copyright information in PMC

Comment in

Lymph node-only metastatic gastric/gastroesophageal junction cancer and efficacy of immunotherapy.
Formica V, Morelli C, Patrikidou A, Shiu KK, Roselli M, Arkenau HT. Formica V, et al. Gastric Cancer. 2020 Nov;23(6):1107-1108. doi: 10.1007/s10120-020-01084-2. Epub 2020 May 18. Gastric Cancer. 2020. PMID: 32424650 No abstract available.

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A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data

Affiliations

A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

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