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

doi:10.1007/s10120-021-01230-4

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 OhKeiko Minashi, Jae Yong Cho, Masahiro Tsuda, Hiroki Sameshima, Li Tzong Chen, Narikazu Boku

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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.

Original language	English
Pages (from-to)	207-217
Number of pages	11
Journal	Gastric Cancer
Volume	25
Issue number	1
DOIs	https://doi.org/10.1007/s10120-021-01230-4
Publication status	Published - 2022 Jan

Bibliographical note

Funding Information:
All authors received grants from Ono Pharmaceutical Co., Ltd., and Bristol-Myers Squibb for the work under consideration for publication. Y-KK reports personal fees from Ono, Bristol-Myers Squibb, Daehwa, Blueprint, Merck, and Astellas, outside the submitted work. MS reports personal fees from Ono, Bristol-Myers Squibb, AstraZeneca, Chugai, Eli Lilly Japan, MSD, Pfizer Japan, and Taiho, outside the submitted work. TS reports personal fees from Ono for the work under consideration for publication; other from Ono (endorsed Department, lecture fee); grants, personal fees, and other from Chugai and Yakult Honsha (endorsed Department, lecture fee); grants and other from Eli Lilly (lecture fee), grants from MSD, Gilead Sciences, Parexel, and Daiichi Sankyo, and Astellas; grants and personal fees from Taiho, personal fees from Takara-Bio, outside the submitted work. M-HR reports honorarium and advisory board fees from Ono, Bristol-Myers Squibb, MSD, Eli Lilly, Taiho, Novartis, Daiichi Sankyo, AstraZeneca, and Daehwa, outside the submitted work. KK reports research funding from Merck & Co., Shionogi, Ono, MSD, Merck Serono, and BeiGene, outside the submitted work. HCC reports grants (research support) from Eli Lilly, GlaxoSmithKline, MSD, Merck Serono, Bristol-Myers Squibb, Ono, Taiho, Amgen, BeiGene, Incyte, and Zymework; personal fees (honoraria) from Merck Serono, Eli Lilly, Foundation Medicine, and Roche; and personal fees (consultation) from Taiho, Celltrion, MSD, Eli Lilly, Quintiles, Bristol-Myers Squibb, Merck Serono, Gloria, BeiGene, Amgen, and Zymeworks, outside the submitted work. J-SC reports personal fees (consultation) from Ono for the work under consideration for publication. KMu reports grants and personal fees from Ono, Sanofi, Taiho, and Amgen; grants from MSD, Daiichi Sankyo, Parexel International, Pfizer, Solasia, and Merck Serono; and personal fees from AstraZeneca, Eli Lilly, Chugai, Takeda, Bristol-Myers Squibb, and Bayer, outside the submitted work. K-HY reports personal fees (honoraria) from Ono, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda, MSD, Eli Lilly, Amgen, and Roche, outside the submitted work. TY reports grants and personal fees (honoraria) from Chugai and Taiho; personal fees (honoraria) from Bristol-Myers Squibb; and personal fees (honoraria and advisory role) from Ono, outside the submitted work. TT reports grants from MSD, Merck Serono, and Chugai; and grants and personal fees from Daiichi Sankyo, Takeda, and Taiho, outside the submitted work. K-WL reports grants from MSD, AstraZeneca/MedImmune, Merck KGaA, Pfizer, BeiGene, ALX Oncology, Zymeworks, MacroGenics, Five Prime Therapeutics, Oncologie, Pharmacyclics, Green Cross Corp, ABLBIO, Y-BIOLOGICS, Genexine, LSK BioPharma, Daiichi Sankyo, Taiho (to his institution for conducting clinical trials), personal fees (consultation) from ISU ABXIS, Bayer and Daiichi Sankyo, outside the submitted work. KC reports personal fees from Ono, Bristol-Myers Squibb, Taiho, and Chugai, outside the submitted work. D-YO reports grants from AstraZeneca outside the submitted work. KMi reports research funding from MSD, Merck Biopharma, Astellas, Taiho., and Daiichi Sankyo, outside the submitted work. HS is an employee of Ono. L-TC reports personal fees from Ono and 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), grants, personal fees and non-financial support from Novartis (study medication and funding support, and honorarium), grants from Pfizer (study funding), personal fees from Eli Lilly (honorarium), grants from Merck Serono (study funding), grants, personal fees and non-financial support from TTY (study medication and funding support, and honorarium), personal fees from PharmaEngine, Shire, MSD, Bristol-Myers Squibb, and Ono (honorarium), grants from OBI (preclinical testing), grants from Polaris (translational Research funding), grants, personal fees and non-financial support from SynCore (study medication and funding support, and honorarium), grants and non-financial support from Celgene (study medication and funding), and personal fees from Five Prime, and Merrimack’ outside the submitted work. NB reports personal fees from Ono and Bristol-Myers Squibb for the work under consideration for publication; grants and personal fees from Taiho and grants from Takeda, outside the submitted work.

Funding Information:
We thank the patients who participated in ATTRACTION-2 and their supportive families. We also thank the investigators and staff at all study sites for their contributions to ATTRACTION-2. Medical writing support, including drafting of the manuscript, assembling of tables, and creation of images based on the authors’ directions, was provided by Masatoshi Esaki, PhD, of Ono Pharmaceutical Co., Ltd., Osaka, Japan, and this study was funded by Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb, Princeton, NJ, USA.

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

Oncology
Gastroenterology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s10120-021-01230-4

Cite this

Kang, Y. K., Morita, S., Satoh, T., Ryu, M. H., Chao, Y., Kato, K., Chung, H. C., Chen, J. S., Muro, K., Kang, W. K., Yeh, K. H., Yoshikawa, T., Oh, S. C., Bai, L. Y., Tamura, T., Lee, K. W., Hamamoto, Y., Kim, J. G., Chin, K., ... Boku, N. (2022). 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. Gastric Cancer, 25(1), 207-217. https://doi.org/10.1007/s10120-021-01230-4

@article{13f41c999ef446c09b2c351f329297b9,

title = "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",

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.",

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

note = "Funding Information: All authors received grants from Ono Pharmaceutical Co., Ltd., and Bristol-Myers Squibb for the work under consideration for publication. Y-KK reports personal fees from Ono, Bristol-Myers Squibb, Daehwa, Blueprint, Merck, and Astellas, outside the submitted work. MS reports personal fees from Ono, Bristol-Myers Squibb, AstraZeneca, Chugai, Eli Lilly Japan, MSD, Pfizer Japan, and Taiho, outside the submitted work. TS reports personal fees from Ono for the work under consideration for publication; other from Ono (endorsed Department, lecture fee); grants, personal fees, and other from Chugai and Yakult Honsha (endorsed Department, lecture fee); grants and other from Eli Lilly (lecture fee), grants from MSD, Gilead Sciences, Parexel, and Daiichi Sankyo, and Astellas; grants and personal fees from Taiho, personal fees from Takara-Bio, outside the submitted work. M-HR reports honorarium and advisory board fees from Ono, Bristol-Myers Squibb, MSD, Eli Lilly, Taiho, Novartis, Daiichi Sankyo, AstraZeneca, and Daehwa, outside the submitted work. KK reports research funding from Merck & Co., Shionogi, Ono, MSD, Merck Serono, and BeiGene, outside the submitted work. HCC reports grants (research support) from Eli Lilly, GlaxoSmithKline, MSD, Merck Serono, Bristol-Myers Squibb, Ono, Taiho, Amgen, BeiGene, Incyte, and Zymework; personal fees (honoraria) from Merck Serono, Eli Lilly, Foundation Medicine, and Roche; and personal fees (consultation) from Taiho, Celltrion, MSD, Eli Lilly, Quintiles, Bristol-Myers Squibb, Merck Serono, Gloria, BeiGene, Amgen, and Zymeworks, outside the submitted work. J-SC reports personal fees (consultation) from Ono for the work under consideration for publication. KMu reports grants and personal fees from Ono, Sanofi, Taiho, and Amgen; grants from MSD, Daiichi Sankyo, Parexel International, Pfizer, Solasia, and Merck Serono; and personal fees from AstraZeneca, Eli Lilly, Chugai, Takeda, Bristol-Myers Squibb, and Bayer, outside the submitted work. K-HY reports personal fees (honoraria) from Ono, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda, MSD, Eli Lilly, Amgen, and Roche, outside the submitted work. TY reports grants and personal fees (honoraria) from Chugai and Taiho; personal fees (honoraria) from Bristol-Myers Squibb; and personal fees (honoraria and advisory role) from Ono, outside the submitted work. TT reports grants from MSD, Merck Serono, and Chugai; and grants and personal fees from Daiichi Sankyo, Takeda, and Taiho, outside the submitted work. K-WL reports grants from MSD, AstraZeneca/MedImmune, Merck KGaA, Pfizer, BeiGene, ALX Oncology, Zymeworks, MacroGenics, Five Prime Therapeutics, Oncologie, Pharmacyclics, Green Cross Corp, ABLBIO, Y-BIOLOGICS, Genexine, LSK BioPharma, Daiichi Sankyo, Taiho (to his institution for conducting clinical trials), personal fees (consultation) from ISU ABXIS, Bayer and Daiichi Sankyo, outside the submitted work. KC reports personal fees from Ono, Bristol-Myers Squibb, Taiho, and Chugai, outside the submitted work. D-YO reports grants from AstraZeneca outside the submitted work. KMi reports research funding from MSD, Merck Biopharma, Astellas, Taiho., and Daiichi Sankyo, outside the submitted work. HS is an employee of Ono. L-TC reports personal fees from Ono and 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), grants, personal fees and non-financial support from Novartis (study medication and funding support, and honorarium), grants from Pfizer (study funding), personal fees from Eli Lilly (honorarium), grants from Merck Serono (study funding), grants, personal fees and non-financial support from TTY (study medication and funding support, and honorarium), personal fees from PharmaEngine, Shire, MSD, Bristol-Myers Squibb, and Ono (honorarium), grants from OBI (preclinical testing), grants from Polaris (translational Research funding), grants, personal fees and non-financial support from SynCore (study medication and funding support, and honorarium), grants and non-financial support from Celgene (study medication and funding), and personal fees from Five Prime, and Merrimack{\textquoteright} outside the submitted work. NB reports personal fees from Ono and Bristol-Myers Squibb for the work under consideration for publication; grants and personal fees from Taiho and grants from Takeda, outside the submitted work. Funding Information: We thank the patients who participated in ATTRACTION-2 and their supportive families. We also thank the investigators and staff at all study sites for their contributions to ATTRACTION-2. Medical writing support, including drafting of the manuscript, assembling of tables, and creation of images based on the authors{\textquoteright} directions, was provided by Masatoshi Esaki, PhD, of Ono Pharmaceutical Co., Ltd., Osaka, Japan, and this study was funded by Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb, Princeton, NJ, USA. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2022",

month = jan,

doi = "10.1007/s10120-021-01230-4",

language = "English",

volume = "25",

pages = "207--217",

journal = "Gastric Cancer",

issn = "1436-3291",

publisher = "Springer Japan",

number = "1",

}

Kang, YK, Morita, S, Satoh, T, Ryu, MH, Chao, Y, Kato, K, Chung, HC, Chen, JS, Muro, K, Kang, WK, Yeh, KH, Yoshikawa, T, Oh, SC, Bai, LY, Tamura, T, Lee, KW, Hamamoto, Y, Kim, JG, Chin, K, Oh, DY, Minashi, K, Cho, JY, Tsuda, M, Sameshima, H, Chen, LT & Boku, N 2022, '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', Gastric Cancer, vol. 25, no. 1, pp. 207-217. https://doi.org/10.1007/s10120-021-01230-4

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. / Kang, Yoon Koo; Morita, Satoshi; Satoh, Taroh et al.

In: Gastric Cancer, Vol. 25, No. 1, 01.2022, p. 207-217.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Exploration of predictors of benefit from nivolumab monotherapy for patients with pretreated advanced gastric and gastroesophageal junction cancer

T2 - post hoc subanalysis from the ATTRACTION-2 study

AU - Kang, Yoon Koo

AU - Morita, Satoshi

AU - Satoh, Taroh

AU - Ryu, Min Hee

AU - Chao, Yee

AU - Kato, Ken

AU - Chung, Hyun Cheol

AU - Chen, Jen Shi

AU - Muro, Kei

AU - Kang, Won Ki

AU - Yeh, Kun Huei

AU - Yoshikawa, Takaki

AU - Oh, Sang Cheul

AU - Bai, Li Yuan

AU - Tamura, Takao

AU - Lee, Keun Wook

AU - Hamamoto, Yasuo

AU - Kim, Jong Gwang

AU - Chin, Keisho

AU - Oh, Do Youn

AU - Minashi, Keiko

AU - Cho, Jae Yong

AU - Tsuda, Masahiro

AU - Sameshima, Hiroki

AU - Chen, Li Tzong

AU - Boku, Narikazu

N1 - Funding Information: All authors received grants from Ono Pharmaceutical Co., Ltd., and Bristol-Myers Squibb for the work under consideration for publication. Y-KK reports personal fees from Ono, Bristol-Myers Squibb, Daehwa, Blueprint, Merck, and Astellas, outside the submitted work. MS reports personal fees from Ono, Bristol-Myers Squibb, AstraZeneca, Chugai, Eli Lilly Japan, MSD, Pfizer Japan, and Taiho, outside the submitted work. TS reports personal fees from Ono for the work under consideration for publication; other from Ono (endorsed Department, lecture fee); grants, personal fees, and other from Chugai and Yakult Honsha (endorsed Department, lecture fee); grants and other from Eli Lilly (lecture fee), grants from MSD, Gilead Sciences, Parexel, and Daiichi Sankyo, and Astellas; grants and personal fees from Taiho, personal fees from Takara-Bio, outside the submitted work. M-HR reports honorarium and advisory board fees from Ono, Bristol-Myers Squibb, MSD, Eli Lilly, Taiho, Novartis, Daiichi Sankyo, AstraZeneca, and Daehwa, outside the submitted work. KK reports research funding from Merck & Co., Shionogi, Ono, MSD, Merck Serono, and BeiGene, outside the submitted work. HCC reports grants (research support) from Eli Lilly, GlaxoSmithKline, MSD, Merck Serono, Bristol-Myers Squibb, Ono, Taiho, Amgen, BeiGene, Incyte, and Zymework; personal fees (honoraria) from Merck Serono, Eli Lilly, Foundation Medicine, and Roche; and personal fees (consultation) from Taiho, Celltrion, MSD, Eli Lilly, Quintiles, Bristol-Myers Squibb, Merck Serono, Gloria, BeiGene, Amgen, and Zymeworks, outside the submitted work. J-SC reports personal fees (consultation) from Ono for the work under consideration for publication. KMu reports grants and personal fees from Ono, Sanofi, Taiho, and Amgen; grants from MSD, Daiichi Sankyo, Parexel International, Pfizer, Solasia, and Merck Serono; and personal fees from AstraZeneca, Eli Lilly, Chugai, Takeda, Bristol-Myers Squibb, and Bayer, outside the submitted work. K-HY reports personal fees (honoraria) from Ono, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda, MSD, Eli Lilly, Amgen, and Roche, outside the submitted work. TY reports grants and personal fees (honoraria) from Chugai and Taiho; personal fees (honoraria) from Bristol-Myers Squibb; and personal fees (honoraria and advisory role) from Ono, outside the submitted work. TT reports grants from MSD, Merck Serono, and Chugai; and grants and personal fees from Daiichi Sankyo, Takeda, and Taiho, outside the submitted work. K-WL reports grants from MSD, AstraZeneca/MedImmune, Merck KGaA, Pfizer, BeiGene, ALX Oncology, Zymeworks, MacroGenics, Five Prime Therapeutics, Oncologie, Pharmacyclics, Green Cross Corp, ABLBIO, Y-BIOLOGICS, Genexine, LSK BioPharma, Daiichi Sankyo, Taiho (to his institution for conducting clinical trials), personal fees (consultation) from ISU ABXIS, Bayer and Daiichi Sankyo, outside the submitted work. KC reports personal fees from Ono, Bristol-Myers Squibb, Taiho, and Chugai, outside the submitted work. D-YO reports grants from AstraZeneca outside the submitted work. KMi reports research funding from MSD, Merck Biopharma, Astellas, Taiho., and Daiichi Sankyo, outside the submitted work. HS is an employee of Ono. L-TC reports personal fees from Ono and 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), grants, personal fees and non-financial support from Novartis (study medication and funding support, and honorarium), grants from Pfizer (study funding), personal fees from Eli Lilly (honorarium), grants from Merck Serono (study funding), grants, personal fees and non-financial support from TTY (study medication and funding support, and honorarium), personal fees from PharmaEngine, Shire, MSD, Bristol-Myers Squibb, and Ono (honorarium), grants from OBI (preclinical testing), grants from Polaris (translational Research funding), grants, personal fees and non-financial support from SynCore (study medication and funding support, and honorarium), grants and non-financial support from Celgene (study medication and funding), and personal fees from Five Prime, and Merrimack’ outside the submitted work. NB reports personal fees from Ono and Bristol-Myers Squibb for the work under consideration for publication; grants and personal fees from Taiho and grants from Takeda, outside the submitted work. Funding Information: We thank the patients who participated in ATTRACTION-2 and their supportive families. We also thank the investigators and staff at all study sites for their contributions to ATTRACTION-2. Medical writing support, including drafting of the manuscript, assembling of tables, and creation of images based on the authors’ directions, was provided by Masatoshi Esaki, PhD, of Ono Pharmaceutical Co., Ltd., Osaka, Japan, and this study was funded by Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb, Princeton, NJ, USA. Publisher Copyright: © 2021, The Author(s).

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85114216883&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85114216883&partnerID=8YFLogxK

U2 - 10.1007/s10120-021-01230-4

DO - 10.1007/s10120-021-01230-4

M3 - Article

C2 - 34480657

AN - SCOPUS:85114216883

SN - 1436-3291

VL - 25

SP - 207

EP - 217

JO - Gastric Cancer

JF - Gastric Cancer

IS - 1

ER -

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this