Efficacy of nab‑paclitaxel vs. Gemcitabine in combination with S‑1 for advanced pancreatic cancer: A multicenter phase II randomized trial

Patients with advanced pancreatic cancer (PC) need a cost‑effective treatment regimen. The present study was designed to compare the efficacy and safety of nab‑paclitaxel plus S‑1 (AS) and gemcitabine plus S‑1 (GS) regimens in patients with chemotherapy‑naïve advanced PC. In this open‑label, multicenter, randomized study named AvGmPC, eligible patients with chemotherapy‑naïve advanced PC were randomly assigned (1:1) to receive AS (125 mg/m2 nab‑paclitaxel, days 1 and 8; 80‑120 mg S‑1, days 1‑14) or GS (1,000 mg/m2 gemcitabine, days 1 and 8; 80‑120 mg S‑1, days 1‑14). The treatment was administered every 3 weeks until intolerable toxicity or disease progression occurred. The primary endpoint was progression‑free survival (PFS). Between December 2018 and March 2022, 101 of 106 randomized patients were treated and evaluated for analysis (AS, n=49; GS, n=52). As of the data cutoff, the median follow‑up time was 11.37 months 95% confidence interval (CI), 9.31‑13.24. The median PFS was 7.16 months (95% CI, 5.19‑12.32) for patients treated with AS and 6.41 months (95% CI, 3.72‑8.84) for patients treated with GS (HR=0.78; 95% CI, 0.51‑1.21; P=0.264). The AS regimen showed a slightly improved overall survival (OS; 13.27 vs. 10.64 months) and a significantly improved ORR (44.90 vs. 15.38%; P=0.001) compared with the GS regimen. In the subgroup analyses, PFS and OS benefits were observed in patients treated with the AS regimen who had KRAS gene mutations and high C‑reactive protein (CRP) levels (≥5 mg/l). The most common grade ≥3 adverse events were neutropenia, anemia and alopecia in the two groups. Thrombocytopenia occurred more frequently in the GS group than in the AS group. While the study did not meet the primary endpoint, the response benefit observed for AS may be suggestive of meaningful clinical activity in this population. In particular, promising survival benefits were observed in the subsets of patients with KRAS gene mutations and high CRP levels, which is encouraging and warrants further investigation. This trial was retrospectively registered as ChiCTR1900024588 on July 18, 2019.