Comparison of chemoradiotherapy and gemcitabine plus nab-paclitaxel for locally advanced pancreatic cancer: an integrated analysis of two randomized phase II trials (JCOG2408A).

[BACKGROUND] Two main therapeutic approaches are currently used for locally advanced pancreatic cancer (LAPC): chemoradiotherapy and systemic chemotherapy. It remains unclear which approach may be more promising, or whether these strategies should be considered alternative or complementary therapeutic options in the management of LAPC. Clinical outcomes and safety were assessed for S-1 plus concurrent radiotherapy (S-1 + RT) and gemcitabine plus nab-paclitaxel (GnP) in patients with LAPC.

[METHODS] We conducted a pooled exploratory analysis of individual patient data derived from two multi-institutional randomized phase II trials conducted by the Japan Clinical Oncology Group (JCOG1106 and JCOG1407). JCOG1106 evaluated S-1 + RT with or without induction chemotherapy. JCOG1407 compared GnP with modified FOLFIRINOX. Based on the results of these trials, S-1 + RT and GnP were selected as promising regimens for chemoradiotherapy and systemic chemotherapy, respectively. The primary endpoint of this study was progression-free survival (PFS). Inverse probability of treatment weighting (IPTW) with stabilized weights was applied based on the propensity score to account for baseline imbalances between the two groups.

[RESULTS] A total of 113 patients were included. After adjustment for patient characteristics, Kaplan–Meier curves showed median PFS, overall survival (OS), and distant metastasis-free survival (DMFS) of 10.2 vs. 9.3 (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.60–1.30), 19.1 vs. 21.2 (HR, 0.73; 95% CI, 0.48–1.11), and 11.5 vs. 13.1 months (HR, 0.73; 95% CI, 0.49–1.08) for S-1 + RT and GnP, respectively. Treatment received after protocol therapy differed substantially: 77.5% in the S-1 + RT group received single-agent chemotherapy, whereas 50.0% in the GnP group, received more intensive regimens, including multi-agent chemotherapy or chemoradiotherapy.

[CONCLUSIONS] GnP may offer advantages in suppressing micrometastatic disease, whereas S-1 + RT may provide benefits in local disease control. These findings suggest that both approaches represent important and complementary therapeutic options for LAPC. Prospective randomized studies are warranted to determine the optimal initial strategy.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12885-026-15699-8.