Association Between Adjuvant Therapy and Survival in Resected Pancreatic Ductal Adenocarcinoma After Different Types and Durations of Neoadjuvant Therapy.

Abstract

Neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) is increasingly being used. The aim of this study was to evaluate the association between type, duration, and sequencing of adjuvant therapy (AT) after NAT and overall survival (OS) in patients with resected PDAC. Patients receiving NAT and resection for PDAC (2010-2019) at two high-volume pancreatic surgery centers were included and stratified into groups on the basis of NAT regimen: gemcitabine-based NAT, 5-fluorouracil (5FU)-based NAT, or switched NAT regimen. The maximally selected rank statistic was used to determine the optimal NAT duration. Univariate and multivariable Cox proportional hazards models were used to assess the association between NAT regimen and OS, and between AT and OS. Of 651 patients, 200 (30.7%) received gemcitabine-based NAT, 362 (56%) received 5FU-based NAT, and 89 (13.7%) switched NAT regimen. Median OS in patients receiving gemcitabine-based NAT was 19 months (95% confidence interval (CI) 17-25 months), compared with 26 months (95% CI 24-31 months) in patients receiving 5FU-based NAT (hazard ratio (HR) 0.81, 95% CI 0.66-0.99, p = 0.04) and 21 months (95% CI 16-26 months) in patients who switched NAT regimen (HR 0.98, 95% CI 0.73-1.29, p = 0.86). Optimal NAT duration was 3.6 months in the complete cohort. Receiving AT was associated with improved survival (HR 0.61, 95% CI 0.43-0.86, p < 0.001), but its association was reduced after a NAT duration of ≥5 months (adjuvant chemotherapy × NAT duration ≥ 5 months: HR 1.50, 95% CI 1.00-2.24, p = 0.048). Patients receiving 5FU-based NAT showed improved survival compared with patients receiving gemcitabine-based NAT before surgery for PDAC. Adjuvant therapy improved survival, particularly in patients with shorter NAT duration.