RINDBeRG Trial Overview
Study Design: An open-label, randomized Phase III trial conducted in Japan from February 2017 to August 2022, involving 402 patients with advanced or recurrent gastric or gastroesophageal adenocarcinoma that had progressed on prior ramucirumab-based chemotherapy. Participants were randomized to receive either: Ramucirumab + irinotecan, or Irinotecan alone Purpose: To assess whether continuing ramucirumab (an anti‑VEGFR‑2 antibody) beyond progression could extend survival outcomes when combined with irinotecan.
Safety: The combination regimen had increased rates of hematologic and gastrointestinal toxicities—including leukopenia, neutropenia, thrombocytopenia, hypoalbuminemia, oral mucositis, malaise, and diarrhea—but was overall manageable.
Interpretation
Progression-Free Survival Benefit: The addition of ramucirumab significantly improved PFS (3.8 vs. 2.8 months; HR ≈ 0.72; P = 0.002). No Overall Survival Benefit: There was no statistically significant improvement in OS, with median OS being comparable between arms (9.4 vs. 8.5 months; HR = 0.91; P = 0.49). Clinical Implication: While adding ramucirumab to irinotecan conferred modest disease control and delayed progression, it did not translate into a meaningful extension of survival.
Summary
The RINDBeRG trial suggests that continuing ramucirumab beyond progression in combination with irinotecan may offer modest improvements in disease control and PFS for patients with ramucirumab-refractory advanced gastroesophageal cancers—but without extending overall survival compared to irinotecan alone. This limits the clinical impact of the regimen as a practice-changing option.