Exploration of predictors of benefit from nivolumab monotherapy for patients with pretreated advanced gastric and gastroesophageal junction cancer: post hoc subanalysis from the ATTRACTION-2 study.

Yoon-Koo Kang, Satoshi Morita, Taroh Satoh, Min-Hee Ryu, Yee Chao, Ken Kato, Hyun Cheol Chung, Jen-Shi Chen, Kei Muro, Won Ki Kang, Kun-Huei Yeh, Takaki Yoshikawa, Sang Cheul Oh, Li-Yuan Bai, Takao Tamura, Keun-Wook Lee, Yasuo Hamamoto, Jong Gwang Kim, Keisho Chin, Do-Youn Oh, Keiko Minashi, Jae Yong Cho, Masahiro Tsuda, Hiroki Sameshima, Li-Tzong Chen, Narikazu Boku

Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2022;25(1):207-217

PMID: 34480657

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Abstract

BACKGROUND

The phase 3 ATTRACTION-2 study demonstrated that nivolumab monotherapy was superior to placebo for patients with pretreated advanced gastric or gastroesophageal junction cancer, but early progression of tumors in some patients was of concern.

METHODS

This post hoc analysis statistically explored the baseline characteristics of the ATTRACTION-2 patients and extracted a single-factor and double-factor combinations associated with early disease progression or early death. In the extracted patient subgroups, the 3-year restricted mean survival times of progression-free survival and overall survival were compared between the nivolumab and placebo arms.

RESULTS

Two single factors (age and peritoneal metastasis) were extracted as independent predictors of early progression, but none of them, as a single factor, stratified patients into two subgroups with significant differences in restricted mean survival time. In contrast, two double-factor combinations (serum sodium level and white blood cell count; serum sodium level and neutrophil-lymphocyte ratio) stratifying patients into two subgroups with significant differences in the restricted mean survival time were extracted. Additional exploratory analysis of a triple-factor combination showed that patients aged < 60 years with peritoneal metastasis and low serum sodium levels (approximately 7% of all patients) might receive less benefit from nivolumab, and patients aged ≥ 60 years with no peritoneal metastasis and normal serum sodium levels might receive higher benefit.

CONCLUSIONS

A combination of age, peritoneal metastasis, and serum sodium level might predict benefit from nivolumab as salvage therapy in advanced gastric or gastroesophageal junction cancer patients, especially less benefit for patients having all three risk factors.

Address: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. [email protected].; Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.; Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan.; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.; Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.; Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.; Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.; Division of Hematology and Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.; Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.; Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan.; Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan.; Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, South Korea.; Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.; Department of Medical Oncology, Faculty of Medicine, Kindai University, Osakasayama, Japan.; Department of Medical Oncology, Kindai University Nara Hospital, Ikoma, Japan.; Division of Hematology and Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.; Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan.; Kyungpook National University School of Medicine, Daegu, South Korea.; Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.; Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea.; Department of Clinical Trial Promotion, Chiba Cancer Center, Chiba, Japan.; Department of Medical Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.; Department of Gastroenterological Oncology, Hyogo Cancer Center, Akashi, Japan.; Medical Affairs, Ono Pharmaceutical, Co. Ltd., Osaka, Japan.; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.; Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

DOI: 10.1007/s10120-021-01230-4

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MeSH Terms: Antineoplastic Agents, Immunological, Esophageal Neoplasms, Esophagogastric Junction, Humans, Middle Aged, Nivolumab, Stomach Neoplasms