FOLFOXIRI and bev achieve high response rate/R0 resections and encouraging PFS in patients with unresectable CLM. Pathological response is known as a surrogate endpoint of survival which is increased by bev. Capecitabine, oxaliplatin, irinotecan and bev (COI-B) is feasible in pts with advanced colorectal cancer. The aim of this phase II study is to assess the perioperative use of this combination in pts with borderline resectable CLM (NCT2086656).
Inclusion criteria: borderline resectability due to technical (need of 2-stage hepatectomy, involvement of > 1 hepatic vein or > 4 segments) and/or biological reasons (> 4 metastases, CEA > 200, synchronicity). Limited resectable extraepatic disease and in situ primary allowed. Primary endpoint: pathological response according to Rubbia-Brandt et al., with a Simon 2-stage design (first step 22 pts; target 46 pts); secondary endpoints: objective response rate (ORR); R0 resection; safety; progression-free and overall survival. Pts received biweekly irinotecan (180 mg/mq) and bev (5 mg/kg) day 1, oxaliplatin (85 mg/mq) day 2 and capecitabine 1000 mg/mq day b.i.d.) days 2-6; 5 cycles pre-operatively (the last without bev) and 4 post-operatively.
We present preliminary data on 36 pts (30 resected, 6 still awaiting). M/F: 21/15, median age 62 years (38-76), synchronous disease in 29 pts (80%), multiple nodules 61% (39% ≥ 4 nodules), N+ primary tumor 50%, CEA > 200 in 4 pts (11%), extrahepatic disease 2.7%, RAS mutation in 53% and no BRAF mutations. Two-stage hepatectomy 3%, ≥ 4 segments involved 43%, > 1 hepatic veins 16%. ORR was 88%, with 3 SD and 1 PD. R0 resection in 24 (80%) pts. TRG 1-2 was observed in 9 (30%), while TRG 3 in 12 pts (40%), i.e. pathological response 70%. Grade ≥ 3 toxicities: diarrhea 2, neutropenia 2, thrombosis 2, fatigue 2, neuropathy 1. At a median follow up of 12 months, we observed 8 relapses and 2 deaths.
COI-B regimen is a feasible perioperative chemotherapy for borderline resectable CLM. This is the first trial to select pathological response as primary endpoint with encouraging activity.
Clinical trial identification
Legal entity responsible for the study
Istituto Nazionale Tumori
All authors have declared no conflicts of interest.