TY - JOUR
T1 - Efficacy of sequential ipilimumab monotherapy versus best supportive care for unresectable locally advanced/metastatic gastric or gastroesophageal junction cancer
AU - Bang, Yung Jue
AU - Cho, Jae Yong
AU - Kim, Yeul Hong
AU - Kim, Jin Won
AU - Bartolomeo, Maria Di
AU - Ajani, Jaffer A.
AU - Yamaguchi, Kensei
AU - Balogh, Agnes
AU - Sanchez, Teresa
AU - Moehler, Markus
N1 - Funding Information:
Y.-J. Bang is a consultant/advisory board member for Bristol-Myers Squibb. Y.H. Kim reports receiving commercial research grants from
Funding Information:
Bristol-Myers Squibb. K. Yamaguchi reports receiving commercial research grants from Boehringer Ingelheim, Bristol, Daiichi-sankyo, Dainippon Sumitomo, Merck, MSD, Ono, Taiho, and Yakurt Honsha, and speakers bureau honoraria from Chugai, Eli Lilly Japan, Merck, Taiho, and Takeda. M. Moehler reports receiving other commercial research support from Amgen, Astrazencea, Bristol-Myers Squibb, MERCK MSD, and Merck Ser-ono, speakers bureau honoraria from Amgen, Bristol-Myers Squibb, MERCK MSD, Merck Serono, Roche, and Taiho, and is a consultant/advisory board member for Amgen, Bayer, Bristol-Myers Squibb, MSD, Nordic, Roche, and Yucult. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
This study was supported by Bristol-Myers Squibb, Inc. Daniel Hutta of Chrysalis Medical Communications, Inc. provided medical writing support funded by Bristol-Myers Squibb.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Purpose: Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte–associated protein-4 interactions, enhances T-cell activation and promotes tumor immunity. This phase II study evaluated the safety and efficacy of ipilimumab monotherapy versus best supportive care (BSC) among patients with advanced/ metastatic gastric or gastroesophageal junction cancer who achieved at least stable disease with first-line chemotherapy. Experimental Design: Eligible patients were randomized to ipilimumab 10 mg/kg every 3 weeks for four doses, then 10 mg/kg every 12 weeks for up to 3 years, or BSC, which could include continuation of fluoropyrimidine until progression or toxicity. The primary endpoint was immune-related progression-free survival (irPFS); secondary endpoints included PFS by modified World Health Organization criteria and overall survival (OS). Results: Of 143 patients screened, 57 were randomized to each arm. irPFS with ipilimumab versus BSC was not improved [2.92 months, 95% confidence interval (CI), 1.61–5.16 vs. 4.90 months, 95% CI, 3.45–6.54, HR ¼ 1.44; 80% CI, 1.09–1.91; P ¼ 0.097], resulting in study cessation. At study closeout, which occurred 8 months after the interim analysis, the median OS durations were 12.7 months (95% CI, 10.5–18.9) and 12.1 months (95% CI, 9.3–not estimable), respectively. Grade 3/4 treatment-related adverse events occurred in 23% of ipilimumab-treated patients, in whom diarrhea (9%) and fatigue (5%) were most frequent, and in 9% of active BSC-treated patients. Conclusions: Although ipilimumab at 10 mg/kg was manageable, it did not improve irPFS versus BSC. However, comparable median OS of approximately 1 year and a favorable safety profile support the investigation of ipilimumab in combination with other therapies for advanced gastric cancer.
AB - Purpose: Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte–associated protein-4 interactions, enhances T-cell activation and promotes tumor immunity. This phase II study evaluated the safety and efficacy of ipilimumab monotherapy versus best supportive care (BSC) among patients with advanced/ metastatic gastric or gastroesophageal junction cancer who achieved at least stable disease with first-line chemotherapy. Experimental Design: Eligible patients were randomized to ipilimumab 10 mg/kg every 3 weeks for four doses, then 10 mg/kg every 12 weeks for up to 3 years, or BSC, which could include continuation of fluoropyrimidine until progression or toxicity. The primary endpoint was immune-related progression-free survival (irPFS); secondary endpoints included PFS by modified World Health Organization criteria and overall survival (OS). Results: Of 143 patients screened, 57 were randomized to each arm. irPFS with ipilimumab versus BSC was not improved [2.92 months, 95% confidence interval (CI), 1.61–5.16 vs. 4.90 months, 95% CI, 3.45–6.54, HR ¼ 1.44; 80% CI, 1.09–1.91; P ¼ 0.097], resulting in study cessation. At study closeout, which occurred 8 months after the interim analysis, the median OS durations were 12.7 months (95% CI, 10.5–18.9) and 12.1 months (95% CI, 9.3–not estimable), respectively. Grade 3/4 treatment-related adverse events occurred in 23% of ipilimumab-treated patients, in whom diarrhea (9%) and fatigue (5%) were most frequent, and in 9% of active BSC-treated patients. Conclusions: Although ipilimumab at 10 mg/kg was manageable, it did not improve irPFS versus BSC. However, comparable median OS of approximately 1 year and a favorable safety profile support the investigation of ipilimumab in combination with other therapies for advanced gastric cancer.
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U2 - 10.1158/1078-0432.CCR-17-0025
DO - 10.1158/1078-0432.CCR-17-0025
M3 - Article
C2 - 28655793
AN - SCOPUS:85032002887
VL - 23
SP - 5671
EP - 5678
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 19
ER -