mFOLFOXIRI + 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)

Abstract

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 þ 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) þ 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 meta-static lesions. Primary endpoint was ORR, secondary endpoints were secondary resec-tion 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 ¼ 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 ¼ 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 ¼ 0.0288, OR 6.400) and in Arm B 60.0% versus 50% (p¼n.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 ¼ 0.0039, OR 6.400; 95%-CI 1.889-21.679) and 60.0% versus 50.0% (p¼ n.s.), respectively. Secondary resections in cohort 2 were 60% (n ¼ 12) and 36.4% (n ¼ 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 ¼ 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. Background: Neoadjuvant chemotherapy has proven valuable in several tumors, but not in colon cancer (CC). The present randomized phase II trial addressed this issue in patients (pts) with locally advanced CC.