Main results of a randomized controlled trial (RNPLS-01): efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 in neoadjuvant therapy for advanced gastric cancer.

Objective/background: The RNPLS-01 trial aimed to evaluate the efficacy and safety of ramucirumab (a VEGFR2 antagonist) combined with nab-paclitaxel, lobaplatin, and S-1 (RNPLS group) versus nab-paclitaxel, lobaplatin, and S-1 alone (NPLS group) in neoadjuvant therapy for advanced gastric cancer, as part of the RNPLS-01 prospective randomized controlled trial.

Methods And Analysis: RNPLS-01 trial enrolled 140 patients with advanced gastric cancer across two cohorts (neoadjuvant therapy: n = 70; conversion therapy: n = 70). This report focuses on the neoadjuvant cohort where patients were randomized 1:1 to receive either RNPLS (n = 35) or NPLS (n = 35). Primary endpoint was pathological complete response (pCR). Secondary endpoints included R0 resection rate, objective response rate (ORR), disease control rate (DCR), and adverse events (AEs).

Results: The RNPLS group demonstrated significant improvements in post-operative T stage (P = 0.008), N stage (P = 0.001), and AJCC clinical stage (P = 0.003) compared to controls. The RNPLS group demonstrated significantly higher pathological complete response (pCR) rates compared to the NPLS group (22.9% vs. 2.9%, P<0.0001). The R0 resection rate was 85.7% in the RNPLS group versus 82.9% in the NPLS group. The RNPLS group achieved a significantly higher objective response rate (ORR) compared to the NPLS group (68.6% vs. 25.7%, P = 0.001), while disease control rates (DCR) were comparable between the two groups (94.3% vs. 77.1%, P = 0.055). Treatment-related adverse events (TRAEs) were confined to grade 1-2 severity, with no grade 3-4 events reported in either group. The RNPLS group showed a TRAE incidence of 80.0%, versus 88.6% in the NPLS group (P = 0.324). Neither group exhibited surgical complications during the study period.

Conclusion: Ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 significantly enhances the pCR rate and ORR in neoadjuvant therapy of locally advanced gastric cancer patients, while maintaining an acceptable safety profile.