Neoadjuvant Chemotherapy with Gemcitabine and S-1 versus Upfront Surgery for Resectable Pancreatic Cancer: Results of the Randomized Phase II/III Prep-02/JSAP05 Trial.

Objective: This randomized phase II/III study evaluated the superiority of neoadjuvant therapy with gemcitabine plus S-1 over upfront surgery for patients with resectable pancreatic ductal adenocarcinoma (PDAC).

Background: Pancreatic ductal adenocarcinoma is a leading cause of cancer mortality that urgently requires better treatment.

Methods: Patients with resectable PDAC (without arterial abutment) were randomly assigned to upfront surgery or neoadjuvant chemotherapy with gemcitabine (1000 mg/m 2 days 1 and 8) and S-1 (40-60 mg orally twice daily, days 1-14 every 3 wk for 2 cycles). Phase II and III primary endpoints were resection rate and overall survival, respectively. UMIN Clinical Trials Registry number: UMIN000009634.

Results: Patients (n=364) were enrolled and randomly allocated to upfront surgery (UPS; n=182) or neoadjuvant gemcitabine plus S-1 (NAC-GS; n=182). Patient demographics and tumor characteristics were balanced between groups. Median overall survival in the UPS and NAC-GS groups was 26.6 (95% confidence interval [CI] 21.5, 31.5) and 37.0 (95% CI 28.6, 43.3) months, respectively. The hazard ratio for mortality in the NAC-GS group compared with the UPS group was 0.73 (95% CI 0.56, 0.95; P =0.018). Median relapse-free survival in the UPS and NAC-GS groups was 11.3 (95% CI 9.41, 13.5) and 14.3 (95% CI 11.7, 17.0) months, respectively. The hazard ratio for relapse in the NAC-GS group compared with the UPS group was 0.77 (95% CI 0.61, 0.98; P =0.030).

Conclusions: The Prep-02/JSAP05 trial results showed that neoadjuvant chemotherapy with gemcitabine plus S-1 significantly extends survival compared with upfront surgery in patients with resectable PDAC.