Multicenter, phase II trial of biweekly S-1, leucovorin (LV), oxaliplatin and gemcitabine (SLOG) in metastatic pancreatic adenocarcinoma (mPDAC): Final report of TCOG T1211 study

Abstract

Background: Our previous studies showed a triplet GOFL regimen consisting of gemcitabine plus modified FOLFOX4 was well‐tolerated and moderate active in advanced PDAC, and the feasibility of replacing infusion 5‐FU/LV with oral S‐1/LV, the SLOG regimen, in a dose‐escalating, phase I study. Herein, we report the phase II results of the SLOG in mPDAC patients. Methods: Patients with chemo‐naïve mPDAC, ECOG PS 0‐1, and 20‐75 y/o of age were eligible. Intravenous fixed‐rate infusion of 800 mg/m2 gemcitabine followed by 2‐ hr infusion of 85mg/m2 oxaliplatin on D1 plus oral S‐1/LV 35/20 mg/m2, twice daily, D1‐D7 were given Q 14 days as a cycle. The primary endpoint was objective response rate (ORR). Simon's optimal two‐stage design was used with estimated p0=25% and p1=40%. Results: Between Jun. 2013 and Oct. 2015, a total of 54 patients were included, with median age of 59 y/o, ECOG PS=1 in 82%, and the presence of liver metastases in 66.7%. At the cut‐off Feb.01, 2017, nine patients remained alive and their median follow‐ up time was 21.3 months. The ORR was partial response in 22 patients (ORR=40.7%, 95% CI, 28‐55%) and stable diseases in 19 patients (35.2%). Long‐term disease control rate (stable disease >16 weeks) was 64.8% (95% CI, 51‐77%). The median progression‐free survival and overall survival was 7.6 (95% CI, 4.4‐10.7) and 11.4 (95% CI, 8.1‐16.3)months, respectively. One‐year and two‐year survival rates were 46% and 17%, respectively. The most common treatment‐related grade 3‐4 adverse events included neutropenia (40.7%), anorexia (14.8%), nausea (11.1%), thrombocytopenia (9.3%), and diarrhea (7.4%). Conclusions: Current study demonstrated SLOG is a highly active regimen with manageable and favorable safety profiles for mPDAC patients. A randomized phase II trial comparing SLOG vs. modified FOLFIRINOX in advanced PDAC patients is ongoing.