Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine: A Pan-European study.

Abstract

e15774 Background: Gemcitabine (GEM) based chemotherapy has been the standard of care for patients with metastatic PDAC with marginal effects on overall survival (OS). In recent years, FOLFIRINOX and Nab-paclitaxel (NAB) + GEM regimens have shown significant survival benefits compared to gemcitabine in clinical trial settings. This study aims to investigate the efficacy of FOLFIRINOX and NAB + GEM versus GEM monotherapy and GEM doublet combinations in real-life settings across different European institutions. Methods: Patients from UK, Sweden, Germany, Italy and Hungary with metastatic PDAC receiving palliative chemotherapy between 2012 and 2015 were included in a retrospective multinational study. Kaplan-Meier method was used for survival analysis. Results: Of the 1089 included patients, 576 (52.9%) were male and 170 (15.6%) underwent primary resection before systemic recurrence. GEM monotherapy was the most commonly used regimen (40.0%; n = 436), followed by combination treatments such as GEM + oxaliplatin, GEM + cisplatin, GEM + capecitabine (24.2%; n = 263), FOLFIRINOX (17,5%; n = 191) and NAB + GEM (7.3%; n = 80). Overall, 6-months and 12-months mortality rate was 48.9% and 72.5%, respectively. The median OS in different groups was: FOLFIRINOX 9.0 months (95% CI 7.1-10.9), NAB + GEM 7.0 months (95% CI 5.8-8.2), other GEM doublet combinations 7.0 months (95% CI 6.0-8.0) and GEM monotherapy 5.0 months (95% CI 4.3-5.7). Compared to GEM monotherapy, intensified chemotherapy either with FOLFIRINOX (p = 0.0001), NAB + GEM (p = 0.02) or GEM doublets (p = 0.0001) was associated with significantly improved survival. Comparison of the different combination regimens was as follows: NAB + GEM vs. FOLFIRINOX (OS: 7.0 vs 9.0 months, p = 0.25), NAB + GEM vs. GEM doublets (OS: 7.0 vs. 7.0 months, p = 0.79) and FOLFIRINOX vs. GEM doublets (OS: 9.0 vs. 7.0 months, p = 0.29). Conclusions: The use of FOLFIRIOX and NAB in clinical routine is variable in Europe. GEM based regimens seem to be the preferred standard of care. Compared to GEM monotherapy, combination treatments improved survival. No significant differences amongst combination therapeutic regimens were identified within our cohort.