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
Journal
Gastric Cancer
Journal Volume
23
Journal Issue
1
Pages
143-153
Date Issued
2020
Author(s)
Satoh T.
Kang Y.-K.
Chao Y.
Ryu M.-H.
Kato K.
Cheol Chung H.
Chen J.-S.
Muro K.
Ki Kang W.
Yoshikawa T.
Oh S.C.
Bai L.-Y.
Tamura T.
Lee K.-W.
Hamamoto Y.
Kim J.G.
Chin K.
Oh D.-Y.
Minashi K.
Cho J.Y.
Tsuda M.
Tanimoto M.
Chen L.-T.
Boku N.
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. ? 2019, The Author(s).
Subjects
Gastric cancer; Gastroesophageal junction?cancer; Nivolumab; Trastuzumab
SDGs
Other Subjects
immunological antineoplastic agent; nivolumab; placebo; trastuzumab; adult; aged; clinical trial; controlled study; double blind procedure; esophagus tumor; female; gastroesophageal junction; human; male; middle aged; mortality; pathology; phase 3 clinical trial; randomized controlled trial; stomach tumor; treatment outcome; very elderly; Adult; 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
Publisher
Springer
Type
journal article