TY - JOUR
T1 - Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial
T2 - a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer
AU - Satoh, Taroh
AU - Kang, Yoon Koo
AU - Chao, Yee
AU - Ryu, Min Hee
AU - Kato, Ken
AU - Cheol Chung, Hyun
AU - Chen, Jen Shi
AU - Muro, Kei
AU - Ki Kang, Won
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 - Tanimoto, Mitsunobu
AU - Chen, Li Tzong
AU - Boku, Narikazu
N1 - Funding Information:
Acknowledgements We thank the patients and their families as well as the investigators and participating study teams for making this study possible. Writing and editorial assistance was provided by Ruhi Ubale, PhD, of Cactus Communications, funded by Ono Pharmaceutical Co., Ltd., Osaka, Japan, and Bristol-Myers Squibb, Inc., Princeton, NJ.
Funding Information:
Funding This study was funded by Ono Pharmaceutical Co., Ltd., Osaka, Japan, and Bristol-Myers Squibb, Inc., Princeton, NJ.
Funding Information:
Conflicts of interest Taroh Satoh received donations for his department from Ono Pharmaceutical, Yakult Honsha, and Chugai Pharmaceutical and received research grants and honoraria from Ono Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Eli Lilly, Bristol Myers Squibb, Merck Serono, Takeda Pharmaceutical, Taiho Pharmaceutical, and MSD. Yoon-Koo Kang is a consultant for Ono Pharmaceutical, Bristol Myers Squibb, Daehwa Pharmaceutical, LSK Biopharma, AstraZeneca, Merck Serono, and Novartis. Min-Hee Ryu received honorarium and served on the advisory boards for Ono Pharmaceutical, Bristol Myers Squibb, MSD, Eli Lilly, Taiho Pharmaceutical, Novartis, and Daehwa Pharmaceutical. Ken Kato received research grants from Ono Pharmaceutical, MSD, Shionogi, Merck Serono, and Beigene. Hyun Cheol Chung received research grants from Ono Pharmaceutical, Eli Lilly, GSK, MSD, Merck Serono, and Taiho Pharmaceutical, honoraria from Merck Serono, Eli Lilly, and Foundation Medicine/Roche, and consultation fees from Taiho Pharmaceutical, Celltrion, MSD, Eli Lilly, Quintiles, BMS, and Merck Serono. Jen-Shi Chen received research grants and consulting fees from Ono Pharmaceutical. Kei Muro received research grants from Ono Pharmaceutical, MSD, Daiichi Sankyo, Kyowa Hakko Kirin, Shionogi Pharmaceutical, and Gilead Sciences and personal fees from Chugai Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, Merck Serono, Eli Lilly, and Yakult Honsha. Kun-Huei Yeh received personal fees from Ono Pharmaceutical, Boehringer Ingelheim, Takeda Pharmaceutical, Bristol Myers Squibb, MSD, Eli Lilly, and Amgen. Takaki Yoshikawa received research grants from Ono Pharmaceutical and Bristol Myers Squibb, Chugai Pharmaceutical, and Taiho Pharmaceutical, honoraria from Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Ono Pharmaceutical, Eli Lilly, Yakult Honsha, Nippon Kayaku, Johnson and Johnson, Covidien, Olympus, Daiichi Sankyo, MSD, and Terumo. Takao Tamura received research grants from Ono Pharmaceutical, Bristol Myers Squibb, MSD, Merck Serono, Daiichi San-kyo, Takeda Pharmaceutical, and Chugai Pharmaceutical and personal fees from Daiichi Sankyo and Takeda Pharmaceutical. Do-Youn Oh received research grants from Astra Zeneca. Yee Chao, Won Ki Kang, Sang Cheul Oh, Li-Yuan Bai, Yasuo Hamamoto, Jong Gwang Kim, Keisho Chin, Keiko Minashi, Jae Yong Cho, Keun-Wook Lee, and Masahiro Tsuda received research grants from Ono Pharmaceutical. Mitsunobu Tanimoto is an employee of Ono Pharmaceutical. Li-Tzong Chen received research grants from Ono Pharmaceutical, Bristol My-ers Squibb, Ministry of Science and Technology, Taiwan, Ministry of Health and Welfare, Taiwan, Novartis, Pfizer, TTY Biopharm, OBI Pharma, Polaris Pharma, Syncore Biotechnology, and Celgene, personal fees from Ono Pharmaceutical, Bristol Myers Squibb, Novartis, Eli Lilly, TTY Biopharm, PharmaEngine, Shire, MSD, Five Prime Therapeutics, AstraZeneca, and Ipsen, and non-financial support from Novartis, TTY Biopharm, PharmaEngine, Syncore, and Celgene. Narikazu Boku received research grants from Ono Pharmaceutical and Taiho Pharmaceutical and personal fees from Ono Pharmaceutical, Chugai Pharmaceutical, Merck Serono, AstraZeneca, and Taiho Pharmaceutical.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Gastric cancer
KW - Gastroesophageal junction cancer
KW - Nivolumab
KW - Trastuzumab
UR - http://www.scopus.com/inward/record.url?scp=85065787461&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065787461&partnerID=8YFLogxK
U2 - 10.1007/s10120-019-00970-8
DO - 10.1007/s10120-019-00970-8
M3 - Article
C2 - 31087200
AN - SCOPUS:85065787461
VL - 23
SP - 143
EP - 153
JO - Gastric Cancer
JF - Gastric Cancer
SN - 1436-3291
IS - 1
ER -