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Gastric Cancer. 2019 May 13. doi: 10.1007/s10120-019-00970-8. [Epub ahead of print]

Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial: a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer.

Author information

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

Abstract

BACKGROUND:

Data on immune checkpoint inhibitor efficacy in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced gastric/gastroesophageal junction (G/GEJ) cancer are lacking. Because HER2 status was not captured in the ATTRACTION-2 trial, we used patients with prior trastuzumab use (Tmab+) as surrogate for HER2 expression status to evaluate the efficacy and safety of nivolumab as third- or later-line therapy in these patients.

METHODS:

In ATTRACTION-2, a randomized, double-blind, placebo-controlled, phase 3 multicenter trial, patients were randomized (2:1) to receive nivolumab (3 mg/kg) or placebo every 2 weeks until disease progression or toxicity requiring study discontinuation. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were assessed.

RESULTS:

Of 493 enrolled patients, 81 (nivolumab, n = 59; placebo, n = 22) were Tmab+ and 412 (nivolumab, n = 271; placebo, n = 141) were Tmab-. In both groups, patients receiving nivolumab showed a longer median OS vs placebo (Tmab+, 8.3 [95% confidence interval, 5.3-12.9] vs 3.1 [1.9-5.3] months, hazard ratio, 0.38 [0.22-0.66]; P = 0.0006; Tmab-, 4.8 [4.1-6.0] vs 4.2 [3.6-4.9] months, 0.71 [0.57-0.88]; P = 0.0022). PFS was longer in both groups receiving nivolumab vs placebo (Tmab+, 1.6 [1.5-4.0] vs 1.5 [1.3-2.9] months, 0.49 [0.29-0.85]; P = 0.0111; Tmab-, 1.6 [1.5-2.4] vs 1.5 [1.5-1.5] months, 0.64 [0.51-0.80]; P = 0.0001).

CONCLUSIONS:

Nivolumab was efficacious and safe as third- or later-line therapy regardless of prior trastuzumab use in patients with advanced G/GEJ cancer.

KEYWORDS:

Gastric cancer; Gastroesophageal junction cancer; Nivolumab; Trastuzumab

PMID:
31087200
DOI:
10.1007/s10120-019-00970-8

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