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). SUMMARY BACKGROUND DATA 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/m2 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). CONCLUSION 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.