HOPS-R01 phase II trial evaluating neoadjuvant S-1 therapy for resectable pancreatic adenocarcinoma

Abstract

Although neoadjuvant therapy (Nac) is recommended for high-risk resectable pancreatic cancer (R-PDAC), evidence regarding specific regimes is scarce. This report aimed to investigate the efficacy of S-1 Nac for R-PDAC. In a multicenter phase II trial, we investigated the efficacy of Nac S-1 (an oral fluoropyrimidine agent containing tegafur, gimeracil, and oteracil potassium) in R-PDAC patients. The protocol involved two cycles of preoperative S-1 chemotherapy, followed by surgery, and four cycles of postoperative S-1 chemotherapy. Two-year progression-free survival (PFS) rates were the primary endpoint. Overall survival (OS) rates and median survival time (MST) were secondary endpoints. Forty-nine patients were eligible, and 31 patients underwent resection following Nac, as per protocol (31/49; 63.3%). Per-protocol analysis included data from 31 patients, yielding the 2-year PFS rate of 58.1%, and 2-, 3-, and 5-year OS rates of 96.8%, 54.8%, and 44.0%, respectively. MST was 49.2 months. Intention-to-treat analysis involved 49 patients, yielding the 2-year PFS rate of 40.8%, and the 2-, 3-, and 5-year OS rates of 87.8%, 46.9%, and 33.9%, respectively. MST was 35.5 months. S-1 single regimen might be an option for Nac in R-PDAC; however, the high drop-out rate (36.7%) was a limitation of this study.

Figure 1

CONSORT diagram of the study flow. A total of 80 patients gave informed consent for the HOPS-R01 trial between January 2014 and October 2015 and were diagnosed with resectable pancreatic ductal adenocarcinoma by a central review of multidetector computed tomography. Neoadjuvant (Nac) S-1 at 80 mg/m² per day was administered for 28 consecutive days followed by a 14-day rest (one cycle). The administration of S-1 was repeated every 6 weeks for two cycles. Of 49 patients who started Nac, 33 patients completed Nac and 31 patients received pancreatectomy. Of 16 Nac-failure patients, 12 patients underwent resection (pancreatectomy).

Figure 2

Kaplan–Meier survival curves of progression-free survival. (A) Intention-to-treat patients (n = 49). (B) Per-protocol patients (neoadjuvant treatment completion and tumor resection, n = 31) and off-protocol patients (neoadjuvant failure or probe laparotomy, n = 18). PFS, progression-free survival; MST, median survival time.

Figure 3

Kaplan–Meier survival curves for overall survival. (A) Intention to treat patients (n = 49). (B) Per-protocol patients (neoadjuvant treatment completion and tumor resection, n = 31) and off-protocol patients (neoadjuvant failure or probe laparotomy, n = 18). OS, overall survival; MST, median survival time.