LBA83 - Neoadjuvant chemotherapy with FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy for borderline resectable and resectable pancreatic cancer (PREOPANC-2): A multicenter randomized controlled trial

Background

The PREOPANC trial demonstrated an overall survival (OS) benefit of neoadjuvant gemcitabine-based chemoradiotherapy compared with upfront surgery in patients with borderline resectable and resectable pancreatic cancer (PDAC). FOLFIRINOX may further improve OS in the neoadjuvant setting.

Methods

This multicenter, phase 3, randomized trial included patients with borderline resectable and resectable PDAC from 19 Dutch centers. Patients received FOLFIRINOX every 14 days for 8 cycles followed by surgery without adjuvant treatment (FFX arm) versus 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions during the second cycle), followed by surgery and 4 cycles of adjuvant gemcitabine (CRT arm). Randomization was stratified by center and resectability status. Primary endpoint was OS. Secondary endpoints included resection rate and serious adverse event (SAE) rate. To demonstrate a hazard ratio (HR) of 0.70 with two-sided α = 0.05 and 80% power, 368 patients (252 events) were needed. HR and 95% CI were estimated using a stratified Cox model.

Results

Between June 2018 and January 2021, 375 patients were randomized to the FFX arm (n=188) or the CRT arm (n=187). Six patients (3 per arm) were excluded because of ineligibility (n=4) or withdrawal of informed consent immediately after randomization (n=2). After a median follow-up of 41.7 months with 254 events, median OS was 21.9 months in the FFX arm and 21.3 months in the CRT arm (HR 0.87; 95% CI 0.68-1.12, p=0.28). Resection rates were 77% in the FFX arm and 75% in the CRT arm (p=0.69). SAE rates were 49% in the FFX arm and 43% in the CRT arm (p=0.26).

Conclusions

Neoadjuvant chemotherapy with FOLFIRINOX did not improve OS compared with neoadjuvant gemcitabine-based chemoradiotherapy in patients with borderline resectable and resectable PDAC.

Clinical trial identification

EudraCT 2017-002036-17.

Editorial acknowledgement

Legal entity responsible for the study

Erasmus MC University Medical Center.

Funding

Dutch Cancer Society and ZonMw.

Disclosure

All authors have declared no conflicts of interest.