BEVACIZUMAB (BV) IN COMBINATION WITH FOLFOXIRI (IRINOTECAN, OXALIPLATIN AND INFUSIONAL 5FU/LV) AS FIRST-LINE TREATMENT OF METASTATIC COLORECTAL CANCER (mCRC): A PHASE II TRIAL BY THE GONO GROUP

Background: A randomized phase III trial comparing the GONO-FOLFOXIRI regimen with FOLFIRI demonstrated that the triple combination improved response rate (RR), progression-free survival (PFS), overall survival (OS) and secondary resection of metastases (Falcone A et al, J Clin Oncol 2007). Several trials demonstrated that the addition of BV to conventional chemotherapy doublets increased treatment efficacy with manageable toxicities. Methods: We conducted a phase II study combining BV (5 mg/kg on d1 until progression) with the GONO-FOLFOXIRI regimen (irinotecan 165 mg/sqm d1, oxaliplatin, 85 mg/sqm d1, l-LV 200 mg/sqm d1, 5FU 3200 mg/sqm 48-h flat continuous infusion starting on d1, repeated every 2 weeks for a maximum of 12 cycles) as first-line treatment of mCRC patients (pts) deemed initially unresectable for metastatic disease. Primary objective was the percentage of pts free of progression at 10 months (from 50% to 70%). Results: We enrolled a total of 57 pts. Main pts characteristics are: M/F = 60%/40%, median age (range) = 61 (34-75) years, ECOG PS 0/1-2 = 68%/32%, primary colon/ rectum = 72%/28%, primary tumor on site = 23%, sites of metastases single/multiple = 58%/42%, liver only metastases = 53%. All pts are assessable for toxicity. Main G3-4 side-effects were: neutropenia 50% (febrile neutropenia 2%), diarrhea 14%, stomatitis 4%, neurotoxicity 2%, deep venous thrombosis 5%, hypertension 11%, cardiac ischemia (G3 only) 2%; G2 bleeding occurred in 1 pt (2%). No toxic deaths have occurred. All pts have been evaluated for response (RECIST) and we observed 7 complete and 37 partial responses (RR= 77%) and 13 stable disease (disease control rate = 100%). Up to now 18 pts (32%) underwent to post-CT surgical resection of metastases with curative intent and 14 R0 resections (25%) have been performed. At a median follow-up of 15.3 months, 28 pts have progressed and median PFS is 13.1+ months with an actuarial PFS at 10 months of 72%. To date 12 pts have died and median OS has not yet been reached. Conclusions: BV can be safely combined with the GONO-FOLFOXIRI regimen without increasing the expected toxicities nor causing unforeseen adverse events. Preliminary data in terms of RR, secondary resection of metastases and PFS are promising and the GONO group is now conducting a phase III study comparing FOLFOXIRI + BV vs FOLFIRI + BV (the TRIBE trial). Updated results will be presented at the meeting