SLOG versus modified FOLFIRINOX as first-line treatment for advanced pancreatic cancer: A randomized phase II trial (TCOG T5217)

OBJECTIVE: A multicenter, randomized phase II trial to compare two first-line triplet treatments for advanced pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients with histologically confirmed advanced PDAC were randomized 1:1 to receive S-1/leucovorin plus oxaliplatin, and gemcitabine (SLOG) or modified FOLFIRINOX (mFOLFIRINOX). Tumor response was assessed every eight weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), safety and biomarker studies. RESULTS: A total of 129 patients (65 SLOG, 64 mFOLFIRINOX) were enrolled. After a median follow-up of 37.7 months, no significant differences were observed between the SLOG and mFOLFIRINOX arms in median PFS (7.5 vs. 6.5 months; p = 0.88), median OS (12.9 vs. 12.1 months), or objective response rate (38.5 % vs. 26.6 %). HRD (homologous recombination deficiency) mutations were found in 14 of 108 profiled patients (12.9 %). Patients with HRD mutations had significantly longer median PFS (11.9 vs. 7.0 months; p = 0.008) and OS (17.7 vs. 11.7 months; p = 0.036). The safety profiles differed: grade 3/4 neutropenia was significantly less common with SLOG (15.4 % vs. 53.1 %; p < 0.001), while SLOG had more grade 3/4 non-hematological toxicities. CONCLUSION: SLOG did not demonstrate superiority in PFS over mFOLFIRINOX, and mFOLFIRINOX therefore remains as one of the preferred first-line standards. Given its lower incidence of severe neutropenia and its convenience with oral S-1, SLOG may warrant further investigation in selected Asian patients with advanced PDAC.