Phase II study of panitumumab (P) in combination with FOLFOXIRI as first-line treatment of metastatic colorectal cancer (mCRC): Activity in molecularly selected patients (pts).

Abstract

3555 Background: GONO-FOLFOXIRI demonstrated higher activity and efficacy compared to FOLFIRI. P with oxaliplatin- or irinotecan-based doublets is feasible and associated with improved activity in KRAS codon 12-13 wild-type pts. BRAF and other RAS rare mutations have been suggested as additional potential biomarkers for anti-EGFR agents. Methods: Pts with untreated unresectable mCRC and wild-type BRAF-RAS genes were enrolled in this GONO multicenter phase II trial of biweekly P 6 mg/kg d1 with a modified FOLFOXIRI regimen (IRI 150 mg/m2 d1, OXA 85 mg/m2 d1, l-LV 200 mg/m2 d1 and 5FU 3000 mg/m2 48-h continuous infusion d1, reduced to 2400 mg/m2 due to grade 3-4 toxicity in 2 of first 3 pts enrolled). Primary end-point was response rate (RR, RECIST Criteria). Based on a two stage Simon’s Minimax design (p0=60%, p1=80%; a=0.05, β =0.2) at least 26 responses on 36 evaluable pts should be observed to satisfy the primary end-point. Results: 37 out of 87 screened pts were enrolled (M/F, 57/43%; median age 63 years, range 33-72; ECOG PS 0/1-2, 76/24%; primary colon/rectum, 70/30%; primary on site, 42%; sites of disease single/multiple, 54/46%; liver only mts, 35%). Among the first 3 pts treated with 5FU 3000 mg/m2, 2 experienced SAEs (1 grade 4 diarrhea and neutropenia; 1 grade 3 diarrhea). Grade 3-4 toxicities observed among the 34 pts treated at the amended dose were: neutropenia 53% (2 febrile neutropenia); diarrhea 32%; stomatitis 15%; neurotoxicity (grade 2-3) 30%; cutaneous rash 24%. Delays or dose reductions were needed only in 9% and 10% of the total 310 cycles, respectively. One SAE (febrile neutropenia and sepsis) resulting in pt death occurred after amendment. 32 partial responses, 4 disease stabilizations and 1 progression were observed, with a RR of 86% (95% CI: 75-97%). 9 pts underwent local procedures on metastases, achieving an R0 resection in 8 and a pathologic complete response in 3 of them. At a median follow-up of 7.4 months mPFS has not been reached. Conclusions: In molecularly selected unresectable pts adding P to FOLFOXIRI resulted in high activity and interesting resection rate. The regimen appears feasible. Further follow-up is needed to assess long-term outcome.