Background: There is no clear consensus on second-line chemotherapy for patients with advanced pancreatic ductal adenocarcinoma (PDAC) after failure of first-line gemcitabine plus nab-paclitaxel (GnP). Objectives: This study aimed to compare the efficacy and safety of oxaliplatin plus S-1 (SOX) versus modified FOLFIRINOX (mFFX) as second-line chemotherapy in this patient population. Design: A retrospective cohort study was conducted. Methods: Patients with advanced PDAC who received second-line SOX or mFFX after GnP failure at Peking Union Medical College Hospital were reviewed. Efficacy (disease control rate (DCR), overall survival (OS), progression-free survival (PFS)), and safety were analyzed. Molecular features were explored in a subgroup using targeted next-generation sequencing (NGS). Results: In total, 113 patients were included (65 SOX, 48 mFFX). The mFFX group had a significantly higher DCR than the SOX group (68.8% vs 40.0%, p = 0.005). Median PFS (4.8 vs 2.4 months, p = 0.001) and OS (10.4 vs 6.1 months, p = 0.001) were significantly longer with mFFX, even after propensity score matching adjustment. However, grade ⩾3 adverse events, particularly severe neutropenia (42.9% vs 13.5%, p = 0.004) and diarrhea (17.1% vs 1.9%, p = 0.031), were more frequent with mFFX. Multivariate analysis confirmed mFFX as an independent predictor for improved PFS (hazard ratio (HR) = 0.52, p = 0.004) and OS (HR = 0.46, p = 0.002). Exploratory NGS analysis in 45 patients suggested ARID1A, INPP4A, NTRK2, and PTPRS alterations may predict poor survival, but did not influence the relative efficacy of either regimen. Conclusion: The mFFX regimen demonstrated superior efficacy over SOX as second-line chemotherapy after GnP failure in advanced PDAC, significantly prolonging PFS and OS. However, this benefit was accompanied by a higher incidence of severe toxicities. Molecular alterations may hold prognostic value but did not guide regimen selection in this study.
Tang et al. (Mon,) studied this question.