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 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/m2 with LV 400 mg/m2 on day 1 and 5‐FU 2400 mg/m2 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.

FOLFIRI3-aflibercept in previously treated patients with metastatic colorectal cancer

“…Drugs and doses are similar to FOLFIRI, except for suppression of the 5-FU bolus. The response rate was higher than that reported for FOLFIRI[ 9 , 10 ]. Based on these results, FOLFIRI3 became the second-line regimen of choice in some centers.…”

“…The median 11.3 mo PFS and median 17.0 mo OS in the irinotecan-naïve population receiving FOLFIRI3-aflibercept as second-line therapy compared favorably to the FOLFIRI-aflibercept combination in the pivotal phase III VELOUR study (response rate 19.8%, median 7.2 mo PFS, median 13.2 mo OS) and the FOLFIRI3 regimen without targeted agent (response rate 17%-23%, median 4-7 mo PFS, median 9-12 mo OS)[ 4 , 9 , 10 , 14 ].…”

The safety and efficacy of Onivyde (irinotecan liposome injection) for the treatment of metastatic pancreatic cancer following gemcitabine-based therapy

“…In the second-line treatment of gastric and GE junction cancers, nanoliposomal irinotecan was compared to irinotecan or docetaxel, with the overall response rate of 13.6% comparable to the 15.9 % response rate observed with docetaxel [9]. In the PEPCOL (PEP02 in colorectal cancer) study in second-line metastatic colorectal cancer, the partial response rates for leucovorin/5-FU/nanoliposomal irinotecan were 14.3% and PFS was 5.0 months, with response rates similar to those in the mFOLFIRI-3 (modified 5-FU/folinic acid and irinotecan) arm of that study [10]. Importantly, the safety and efficacy of the combination nanoliposomal irinotecan arm in the PECOL study served as the basis for the inclusion of such combination in the presently discussed NAPOLI-1 trial.…”

Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI‐1 study

“…A third arm comprised nal‐IRI monotherapy (120 mg/m 2 irinotecan hydrochloride trihydrate salt, equivalent to 100 mg/m 2 irinotecan free base every 3 weeks). Although initially designed to compare nal‐IRI monotherapy with 5‐FU/LV alone, the NAPOLI‐1 trial was amended to add the nal‐IRI+5‐FU/LV arm when safety data on the combination became available . Patients were randomized 1:1:1.…”