1* - Modified FOLFOXIRI (mFOLFOXIRI) plus cetuximab (cet), followed by cet or bevacizumab (bev) maintenance, in RAS/BRAF wt metastatic colorectal cancer (mCRC): the phase II randomized MACBETH trial by GONO

Abstract

Background: MACBETH trial aimed at evaluating the efficacy of a 4 months-induction with mFOLFOXIRI plus cet in RAS/BRAF wt mCRC patients (pts), followed by two different maintenance strategies: continuing cet or switching to bev. Although the primary endpoint, 10 months-Progression Free Rate, was not met in any treatment arm, the induction treatment was very active and the safety profile was acceptable. Methods: Unresectable and untreated mCRC pts aged between 18 and 75 ys were eligible if their tumors were RAS/BRAF wt at central screening. Pts were randomized to receive up to 8 cycles of mFOLFOXIRI + cet (cet 500 mg/sqm, iri 130 mg/sqm, oxa 85 mg/sqm, I-LV 200 mg/sqm, 5FU 2400 mg/sqm in 48h q2w), followed by cet (arm A) or bev (arm B) until progression (PD). Results: Between Nov 2011 and Feb 2015, 323 pts from 21 Italian centers were screened and 116 pts were included in the modified intention to treat (mITT) population (arm A/B N = 59/57). Response rate was 72% (arm A/B 68%/75%) in the mITT population and 76% in 109 evaluable pts. Early response rate was 74% (arm A/B 74%/74%), and median deepness of response was 53% (arm A/B 49%/56%). Resection rate was 38% (arm A/B 46%/30%) in the mITT population and 65% (arm A/B 71%/58%) in the liver-only subgroup (N = 52, arm A/B 28/24). One-third of pts with liver-only disease who achieved resection underwent re-resection with radical intent after PD. At a median follow-up of 25.5 months, 100 pts (arm A/B 48/52) progressed. Median PFS in arm A and B was 11.2 and 9.3 months, respectively (HR: 0.78 [0.52-1.18). Among patients who received at least one cycle of maintenance (arm A/B N = 36/41) median PFS was 14.0 and 10.7 months (HR: 0.63 [0.37-1.08]), and median PFS from the beginning of maintenance was 8.6 and 5.6 months (HR: 0.69 [0.40-1.17]). Conclusions: mFOLFOXIRI + cet demonstrated remarkable activity, leading to high resection rate. Re-resections were achievable after PD in a considerable subgroup of pts with liver-only disease, supporting the long-term impact of active upfront regimens. Continuing cet as maintenance until PD seems to positively affect PFS. OS results will be presented.