Randomized phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus FTD/TPI for previously treated patients with advanced gastric or gastroesophageal junction adenocarcinoma: Final analysis of RETRIEVE study (WJOG 15822G).

4038 Background: Promising activity of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) has been reported in single-arm phase II trials as third- or later-line treatment for advanced gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma (Lancet Gastroenterol Hepatol. 2021; 6: 209-217). We previously reported the primary analysis of the RETRIEVE study at ASCO-GI 2026, which demonstrated no significant difference in progression-free survival (PFS; median 2.69 vs 2.07 months) between FTD/TPI plus RAM and FTD/TPI alone. Here, we present the final analysis, including overall survival (OS) as a key secondary endpoint, along with updated results of other endpoints. Methods: RETRIEVE study is a multicenter, prospective, open-label, randomized phase II trial comparing FTD/TPI plus RAM versus FTD/TPI alone in patients with unresectable or recurrent GC or GEJ adenocarcinoma who were refractory or intolerant to fluoropyrimidine, taxane, or irinotecan, and refractory to RAM. Treatment is repeated every 4 weeks until disease progression or unacceptable toxicity. Key eligibility criteria include age of ≥20 years; ECOG performance status of 0 or 1, and at least a measurable lesion per RECIST 1.1. Results: Between January 2023 and June 2024, 111 patients were randomly assigned to receive FTD/TPI plus RAM (n = 56) or FTD/TPI alone (n = 55). At a median follow-up of 18.4 months, median OS was 6.08 months in the combination arm and 7.36 months in the monotherapy arm (hazard ratio [HR], 1.233; 95% CI, 0.817–1.862; P = 0.318). The proportion of patients who received subsequent treatment was 64.3% in the combination arm and 56.4% in the monotherapy arm. In the updated analysis, median PFS was 2.69 months in the combination arm and 2.07 months in the monotherapy arm (HR, 1.010; 80% CI, 0.781–1.307; P = 0.959). Objective response rate (ORR; 5.4% vs 9.1%, P = 0.489) and disease control rate (DCR; 50.0% vs 47.3%, P = 0.850) were consistent with the primary analysis. No novel adverse events were identified from the primary analysis. Any grade of n (49.1% vs 25.5%) and diarrhea (29.1% vs 14.5%) were more frequently observed in the combination arm than in the monotherapy arm. Conclusions: The final analysis demonstrated that FTD/TPI plus RAM did not provide a significant OS benefit compared with FTD/TPI alone in third- or later-line treatment for advanced GC and GEJ adenocarcinoma. Updated results of PFS, tumor response, and safety profile were consistent with the primary analysis. Clinical trial information: jRCTs041220120.