Mfolfoxiri Plus Panitumumab Versus Folfoxiri As First-Line Treatment In Patients With Ras Wild-Type Metastatic Colorectal Cancer M(Crc): A Randomized Phase Ii Volfi Trial Of The Aio (Aio-Krk0109).

Background: Triple chemotherapy with an anti-EGFR reported promising activity with some safety concerns in single arm phase II trials. The randomized VOLFI trial evaluated activity and safety of mFOLFOXIRI + panitumumab versus FOLFOXIRI in ECOG 0-1, primarily non-resectable mCRC patients. Methods: Prospective 2:1 randomized, multi-center, phase II trial comparing mFOLFOXIRI (Oxaliplatin 85 mg/m2, Irinotecan 150 mg/m2, 5-FU 3000mg/m2 cont. 48h, LV 200 mg/m2) + Panitumumab 6 mg/KG (arm A) with FOLFOXIRI (Ox 85 mg/m2, Iri 165 mg/m2, 5-FU 3200mg/m2 cont. 48h, LV 200 mg/m2; arm B), both arms q2w. Cohort 1: irresectable mCRC; cohort 2: chance of secondary resection of metastatic lesions. Primary endpoint was ORR, secondary endpoints were secondary resection rate (cohort 2), DCR, PFS, OS, toxicity, quality of life. Financially supported by an unrestricted grant from Amgen. Results: A total of 96 patients were randomized (63 arm A, 33 arm B). In arm A and B 20 (31.7%) and 11 (33.3%) patients belonged to cohort 2, respectively. ORR was 85.7% in arm A and 54.5% in arm B (p = 0.0013, OR 5.000; 95%-CI 1.870-13.370). DCR was 96.8% in arm A and 78.8% in arm B (p = 0.0071, OR 8.212). In arm A and B 53 (84,1%) and 25 (75.8%) tumors were left sided, 10 (15.9%) and 6 (18.2%) were located in the right colon, respectively. ORR in Arm A was 90.6% versus 60.0% (p = 0.0288, OR 6.400) and in Arm B 60.0% versus 50% (p=n.s.) for left and right located CRC, respectively. ORR between arms A and B comparing left and right sided CRC was 90.6% versus 60.0% (p = 0.0039, OR 6.400; 95%-CI 1.889-21.679) and 60.0% versus 50.0% (p= n.s.), respectively. Secondary resections in cohort 2 were 60% (n = 12) and 36.4% (n = 4) in arms A and B, respectively. Serious adverse advents grade 3-5 occured in 45.3% and 24.2% in arms A and B, respectively (p = 0.0496). Conclusions: mFOLFOXIRI plus panitumumab results in significantly higher response rates compared to FOLFOXIRI in RAS wild-type mCRC. Response rates, however, are differential according to tumor sidedness. High secondary resection rates were observed. Toxicity is manageable in younger fit patients with ECOG 0-1. PFS, OS, QL and TR data are still immature and will be presented at the meeting. Clinical trial identification: NCT01328171 Legal entity responsible for the study: AIO Funding: Amgen Disclosure: M. Geissler: Honoraria and advisory board from Amgen All other authors have declared no conflicts of interest.