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

Taroh Satoh, Yoon Koo Kang, Yee Chao, Min Hee Ryu, 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 MinashiJae Yong Cho, Masahiro Tsuda, Mitsunobu Tanimoto, Li Tzong Chen, Narikazu Boku

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)143-153
Number of pages11
JournalGastric Cancer
Volume23
Issue number1
DOIs
Publication statusPublished - 2020 Jan 1

Keywords

  • Gastric cancer
  • Gastroesophageal junction cancer
  • Nivolumab
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

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    Satoh, T., Kang, Y. K., Chao, Y., Ryu, M. H., Kato, K., Cheol Chung, H., Chen, J. S., Muro, K., Ki Kang, W., Yeh, K. H., Yoshikawa, T., Oh, S. C., Bai, L. Y., Tamura, T., Lee, K. W., Hamamoto, Y., Kim, J. G., Chin, K., Oh, D. Y., ... Boku, N. (2020). 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. Gastric Cancer, 23(1), 143-153. https://doi.org/10.1007/s10120-019-00970-8