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Background: Although gemcitabine plus nab-paclitaxel (Gem-NabP), modified FOLFIRINOX (mFOLFIRINOX), and NALIRIFOX are all recommended by current clinical guidelines as first-line treatment options for metastatic pancreatic ductal adenocarcinoma (mPDAC), the optimal regimen in real-world practice remains uncertain. Objective: To compare the efficacy and safety of different first-line chemotherapy regimens for mPDAC. Design: This was a single-center retrospective study. We included 215 patients with previously untreated mPDAC who received first-line chemotherapy at our institution between September 2023 and February 2025: Gem-NabP (n = 121), mFOLFIRINOX ( n = 55), and NALIRIFOX ( n = 39). Methods: The primary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR), while overall survival (OS) was a secondary endpoint. Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1. Survival outcomes were analyzed using the Kaplan–Meier method and Cox proportional hazards models. Exploratory subgroup analyses were also performed. Results: NALIRIFOX showed the most favorable efficacy profile, with a median PFS of 9.0 months, a 6-month OS rate of 92.0%, an ORR of 30.77%, and a DCR of 89.74%, compared with 3.5 months, 74.6%, 18.18%, and 64.46% in the Gem-NabP group and 5.0 months, 82.6%, 16.36%, and 76.36% in the mFOLFIRINOX group, respectively (PFS, p < 0.001; ORR, p = 0.171; DCR, p = 0.007). Median OS was not reached in any group, and the between-group difference in OS was not statistically significant ( p = 0.062). In multivariable Cox analyses, both mFOLFIRINOX and NALIRIFOX remained associated with lower risks of disease progression and death than Gem-NabP, whereas alcohol consumption was independently associated with poorer survival. Toxicities were manageable across regimens, with most adverse events being Grade 1-2 and no treatment-related deaths. Grade ⩾3 adverse events were infrequent and generally comparable among groups. Exploratory analyses suggested a more favorable response distribution with NALIRIFOX in patients with mild-to-moderate cancer pain and those with tumors in the pancreatic head, neck, or tail. Conclusion: In this retrospective single-center cohort, NALIRIFOX was associated with longer PFS and favorable short-term survival, with manageable toxicity. These findings require validation in larger prospective multicenter studies.
Wang et al. (2026) studied this question.