Abstract

Aim: This study primarily aimed to assess the efficacy of second-line ramucirumab (RAM) plus paclitaxel (PTX) in advanced gastric and gastroesophageal junction (GEJ) cancers and to compare its outcomes with RAM+PTX plus immune checkpoint inhibitor (ICI) in real-world practice. The secondary objective was to assess the safety of RAM+PTX (±ICI) and to explore the its efficacy in later-line settings.
Materials and Methods: In this single-center study, we retrospectively analyzed clinical and pathological data from patients with advanced gastric/GEJ cancer treated with RAM+PTX, with or without an ICI, in second-line or later settings between January 2018 and September 2024. Efficacy was evaluated based on objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Efficacy outcomes were analyzed by treatment line.
Results: We identified 46 patients (54.3% female) who received RAM+PTX (±ICI). In the second-line setting, 27 patients (58.7%) received RAM+PTX, and 10 patients (21.7%) received RAM+PTX plus nivolumab. ORRs were 18.5% and 30.0% (p = 0.66), DCRs were 55.6% and 80% (p = 0.26), respectively. The addition of nivolumab did not significantly improve survival outcomes (median PFS 4.3 vs. 3.1 months, HR 0.93, 95% CI 0.44 – 1.98, p = 0.85, median OS 7.8 vs. 9.6 months, HR 0.82, 95% CI 0.35 – 1.91, p = 0.64). Age ≥50 years (HR 2.90, 95% CI 1.24 – 6.78, p = 0.014) and the presence of ascites (HR 2.86, 95% CI 1.14 – 7.16, p = 0.025) were independently associated with poorer OS.
Conclusions: The real-world efficacy of RAM+PTX as second-line therapy in advanced gastric/GEJ cancers aligns with results from randomized trials, though grade ≥3 adverse events were more frequent. While adding nivolumab did not confer a statistically significant benefit, a numerical improvement in ORR and DCR suggests potential value that warrants further prospective evaluation.

Key words: Immunotherapy, stomach neoplasms, VEGFR-2, ramucirumab