1L nab-paclitaxel + S-1 extends PFS and OS vs nab-paclitaxel + gemcitabine in Chinese patients with advanced pancreatic cancer

A phase II trial demonstrated significantly longer progression-free survival (PFS) and overall survival (OS) in Chinese patients with advanced pancreatic cancer (APC) who received first-line treatment with nab-paclitaxel plus S-1 (AS) vs nab-paclitaxel plus gemcitabine (AG).

While multidrug chemotherapy regimens, such as fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) and AG, improve survival in patients with metastatic APC vs gemcitabine alone, the increased toxicity of these regimens limits their use and an unmet need for treatments with manageable tolerability remains.

S-1 is an oral fluoropyrimidine derivative with established efficacy and good tolerability in APC. [Cancer Chemother Pharmacol 2013;72:845-852] It is approved for various cancers, including pancreatic and gastric cancers, in Japan and other parts of Asia and for gastric cancer in Europe. The majority of S-1 randomized clinical trials (RCTs) to date have been conducted in Japanese patients. [J Clin Oncol 2013;31:1640-1648; Lancet 2016;388:248-257]

The present multicentre, phase II RCT was conducted in 62 Chinese patients with APC, who were treated with AS (n=32; median age, 58.5 years; male, 78.13 percent) or AG (n=30; median age, 56.0 years; male, 66.67 percent) between July 2019 and September 2022. [Oncologist 2024;29:e1406-e1418] At the preplanned interim data analysis cutoff (March 2023), 16 patients (AS, n=10; AG, n=6) completed the planned therapeutic protocol. The remaining 46 patients (AS, n=22; AG, n=24) discontinued treatment early due to disease progression (4 vs 6), adverse events (AEs; 9 vs 5), chemotherapy delay >21 days (3 vs 0), investigator discretion (1 vs 4), patient choice (5 vs 7), and death (0 vs 2).

With a median follow-up of 8.36 months at preplanned interim analysis and after 48 events, median PFS in the AS group was significantly longer than in the AG group (8.48 vs 4.47 months; hazard ratio [HR], 0.402; 95 percent confidence interval [CI], 0.223–0.726; p=0.002). After 30 deaths, median OS was also significantly longer in the AS vs AG group (13.73 vs 9.59 months; HR, 0.226; 95 percent CI, 0.103–0.497; p<0.001). The researchers suggested that the survival benefits observed may be due to the synergistic antitumour effects of nab-paclitaxel and S-1 previously reported in a preclinical model. [J Surg Oncol 2016;113:413-419]

In the evaluable population, the objective response rate assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was 37.50 vs 6.67 percent in the AS vs AG group (p=0.005). Among responders, median duration of response was 7.98 months in the AS group and 2.94 months in the AG group.

AEs of any grade occurred in 87.5 and 83.33 percent of patients in the AS and AG group, respectively. The most frequently reported AEs of any grade in the AS and AG groups were haematologic events, including anaemia (62.50 vs 53.33 percent), leukopenia (56.25 vs 33.33 percent), neutropenia (59.38 vs 33.33 percent), and thrombocytopenia (43.75 vs 36.67 percent). The most common grade 3–4 AEs in the two groups were neutropenia (40.63 vs 20.00 percent) and leucopenia (25.00 vs 6.67 percent). No treatment-related deaths occurred in either group. “It is worth noting that the AEs observed in both treatment groups were generally of grade 1–2 and resolved without specific treatment. AS was generally well-tolerated and had a safety profile comparable to AG,” added the researchers.

“Our findings suggest that the first-line AS regimen might be a convenient and reasonable alternative to AG in treatment of APC,” they concluded.