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.

TitleExploratory 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.
Publication TypeJournal Article
Year of Publication2020
AuthorsSatoh, T, Kang, Y-K, Chao, Y, Ryu, M-H, Kato, K, Chung, HCheol, Chen, J-S, Muro, K, Kang, WKi, Yeh, K-H, Yoshikawa, T, Oh, SCheul, Bai, L-Y, Tamura, T, Lee, K-W, Hamamoto, Y, Kim, JGwang, Chin, K, Oh, D-Y, Minashi, K, Cho, JYong, Tsuda, M, Tanimoto, M, Chen, L-T, Boku, N
JournalGastric Cancer
Volume23
Issue1
Pagination143-153
Date Published2020 01
ISSN1436-3305
KeywordsAdult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological, Double-Blind Method, Esophageal Neoplasms, Esophagogastric Junction, Female, Humans, Male, Middle Aged, Nivolumab, Placebos, Stomach Neoplasms, Trastuzumab, Treatment Outcome
Abstract

<p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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).</p><p><b>CONCLUSIONS: </b>Nivolumab was efficacious and safe as third- or later-line therapy regardless of prior trastuzumab use in patients with advanced G/GEJ cancer.</p>

DOI10.1007/s10120-019-00970-8
Alternate JournalGastric Cancer
PubMed ID31087200
PubMed Central IDPMC6942596
Grant ListNA / / Funded by Ono Pharmaceutical Co., Ltd., Osaka, Japan, and Bristol-Myers Squibb, Inc., Princeton, NJ. / International