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

Benoist Chibaudel, Frédérique Maindrault-Gœbel, Jean-Baptiste Bachet, Christophe Louvet, Ahmed Khalil, Olivier Dupuis, Pascal Hammel, Marie-Line Garcia, Mostefa Bennamoun, David Brusquant, Christophe Tournigand, Thierry André, Claire Arbaud, Annette K Larsen, Yi-Wen Wang, C Grace Yeh, Franck Bonnetain, Aimery de Gramont, Benoist Chibaudel, Frédérique Maindrault-Gœbel, Jean-Baptiste Bachet, Christophe Louvet, Ahmed Khalil, Olivier Dupuis, Pascal Hammel, Marie-Line Garcia, Mostefa Bennamoun, David Brusquant, Christophe Tournigand, Thierry André, Claire Arbaud, Annette K Larsen, Yi-Wen Wang, C Grace Yeh, Franck Bonnetain, Aimery de Gramont

Abstract

A multicenter, open-label, noncomparative, randomized phase II study (PEPCOL) was conducted to evaluate the efficacy and safety of the irinotecan or PEP02 (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 PEP02 with LV/5-FU (FUPEP; PEP02 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.

Keywords: Colorectal cancer; MM398; PEP02; nanoliposomal irinotecan; phase II.

© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Participant flow.
Figure 2
Figure 2
Waterfall plots showing the best response to the FOLFIRI arm (A) and the FUPEP arm (B) [arm A, light: FOLFIRI‐1; dark, mFOLFIRI‐3].

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