S-1 plus oxaliplatin versus modified FOLFIRINOX for advanced pancreatic adenocarcinoma after gemcitabine plus nab-paclitaxel failure.

ABSTRACT:

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.

SUBMITTER: Tang H 

PROVIDER: S-EPMC12464396 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature