PEPCOL: a GERCOR randomized phase II study of nanoliposomal irinotecan PEP02 (MM‐398) or irinotecan with leucovorin/5‐fluorouracil as second‐line therapy in metastatic colorectal cancer

Abstract A multicenter, open‐label, noncomparative, randomized phase II study ( PEPCOL ) was conducted to evaluate the efficacy and safety of the irinotecan or PEP 02 ( MM ‐398, nanoliposomal irinotecan) with leucovorin ( LV )/5‐fluorouracil (5‐ FU ) combination as second‐line treatment in patients with metastatic colorectal cancer ( mCRC ). Patients with unresectable mCRC who had failed one prior oxaliplatin‐based first‐line therapy were randomized toirinotecan with LV /5‐ FU ( FOLFIRI ) or PEP 02 with LV /5‐ FU ( FUPEP ; PEP 02 80 mg/m 2 with LV 400 mg/m 2 on day 1 and 5‐ FU 2400 mg/m 2 on days 1–2). Bevacizumab (5 mg/kg, biweekly) was allowed in both arms. The primary endpoint was 2‐month response rate ( RR ). Fifty‐five patients were randomized ( FOLFIRI , n = 27; FUPEP , n = 28). In the intent‐to‐treat population ( n = 55), 2‐month RR response rate was observed in two (7.4%) and three (10.7%) patients in the FOLFIRI and FUPEP arms, respectively. The most common grade 3–4 adverse events reported in the respective FOLFIRI and FUPEP arms were diarrhea (33% vs. 21%), neutropenia (30% vs. 11%), mucositis (11% vs. 11%), and grade 2 alopecia (26% vs. 25%). FUPEP has activity and acceptable safety profile in oxaliplatin‐pretreated mCRC patients.