Rechallenge With Immune Checkpoint Inhibitors in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

While immune checkpoint inhibitors (ICIs) are widely used for advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, most patients still experience disease progression, and subsequent treatment options are limited. ICI rechallenge strategies have been thoroughly studied in other cancers, but evidence in gastric cancer remains scarce. This study evaluated the efficacy, prognostic factors, and safety of ICI rechallenge in advanced G/GEJ adenocarcinoma.

Patients who received ICI rechallenge between November 2019 and April 2025 after progression on first-line ICI-based therapy were analyzed. Primary endpoints included progression-free survival (PFS2) and overall survival after rechallenge (OS2). Secondary endpoints included the confirmed objective response rate (ORR), disease control rate (DCR), and safety.

A total of 96 patients were included. The median age was 63.5 years (range, 29-82). At a median follow-up of 15.17 months, the confirmed ORR with rechallenge was 23.0% (22/96), and the DCR was 63.5% (61/96). The median PFS2 was 4.67 months (range, 0.73-25.37), and the median OS2 was 11.17 months (range, 0.87-36.73). Multivariate analysis identified metastatic organs >2 and serum albumin (ALB) ≤ 38.9 g/L as independent poor prognostic factors for OS2, whereas a history of gastrectomy and an ICI-free interval ≤1.2 months were independent favorable prognostic factors for PFS2. Grade ≥3 adverse events (AEs) occurred in 24.0% (23/96) of patients during the rechallenge phase, and immune-related adverse events (irAEs) were observed in 28.1% (27/96).

ICI rechallenge showed antitumor activity and encouraging survival benefits with an acceptable toxicity profile in patients with advanced G/GEJ adenocarcinoma.