Randomized phase II trial of chemoradiotherapy with S-1 versus combination chemotherapy with gemcitabine and S-1 as neoadjuvant treatment for resectable pancreatic cancer (JASPAC 04).

Abstract

724 Background: Although neoadjuvant treatment (NAT) has been widely employed for resectable pancreatic ductal adenocarcinoma (PDAC), it is still unclear what kind of regimen is recommended. The aim of the study is to investigate which chemoradiotherapy (CRT) with S-1 or combination chemotherapy with gemcitabine (GEM) and S-1 is more promising as NAT for resectable PDAC in terms of effectiveness and safety. Methods: Patients with resectable PDAC were enrolled and randomly assigned into either CRT group or chemotherapy group. In the CRT group, a total radiation dose of 50.4 Gy in 28 fractions was administered and S-1, at a dose of 30, 40 or 50 mg according to the body surface area, was orally provided twice a day on the same day of irradiation. In the chemotherapy group, GEM was intravenously administered at a dose of 1000 mg/m2 on day 1 and 8 and S-1 was orally provided at a dose of 30, 40 or 50 mg according to the body surface area twice daily on day 1 to 14 followed by one week reset. Patients in the chemotherapy group received two cycles of this regimen. Surgery was performed between 15 and 56 days after the last day of NAT. The primary endpoint was 2-year progression-free survival (PFS) rate. With 50 patients in each group, the study had 80% power assuming a threshold 2-year PFS rate of 25% and an expected 2-year PFS rate of 40% at 0.05 one-sided alpha. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894. Results: From April 2014 and April 2017, 103 patients were enrolled from 11 institutions in Japan. One was excluded because of ineligibility, therefore 51 patients in CRT group and 51 patients in chemotherapy group constituted the intention-to-treat analysis. The 2-year PFS rate was 45% (90% CI, 33-60%) in the CRT group and 55% (43-65%) in the chemotherapy group (p = 0.52). The hazard ratio for chemotherapy to CRT was 0.78 (0.46-1.31). The median survival time was 37.7 (95% CI, 30.3-NE) in the CRT group and NE (29.9-NE) in the chemotherapy group (p = 0.30). There was no treatment-related death in both groups. Conclusions: Combination chemotherapy with GEM and S-1 may be more promising compared with CRT with S-1 as NAT for resectable PDAC. Clinical trial information: UMIN000014894.