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 (GC), as part of the RNPLS-01 prospective randomized controlled trial.

METHODS AND ANALYSIS: RNPLS-01 trial enrolled 140 patients with advanced GC 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 (American Joint Committee on Cancer) clinical stage ( P = 0.003) compared to controls. The RNPLS group demonstrated significantly higher 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 ORR compared to the NPLS group (68.6% vs. 25.7%, P = 0.001), while DCRs 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 GC patients, while maintaining an acceptable safety profile.