FOLFOXIRI in combination with panitumumab as first-line treatment in quadruple wild-type (KRAS, NRAS, HRAS, BRAF) metastatic colorectal cancer patients: a phase II trial by the Gruppo Oncologico Nord Ovest (GONO)

摘要: Abstract Background The FOLFOXIRI regimen developed by the Gruppo Oncologico Nord Ovest (GONO) demonstrated higher activity and efficacy compared with FOLFIRI in metastatic colorectal cancer (mCRC). Panitumumab is effective some patients KRAS codon 12–13 wild-type mCRC. 61, HRAS, NRAS, BRAF V600E mutations might predict resistance to anti-epidermal growth factor receptor antibodies. Patients methods We conducted a phase II study evaluating combination of panitumumab (6 mg/kg on day 1) slightly modified GONO-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 folinate 200 mg/m2 1, followed fluorouracil 3000 as 48-h continuous infusion starting repeated every 2 weeks first-line treatment KRAS, NRAS (codon 12–13–61), unresectable mCRC patients. Fluorouracil dose was reduced 2400 after two first three reported grade 3–4 diarrhoea (in one case febrile neutropenia). Induction scheduled for maximum 12 cycles, ± fluorouracil/folinate maintenance until progression. Primary end point overall response rate (ORR). Results Eighty-seven were screened 37 enrolled. Thirty-three achieved an objective (ORR: 89%; 95% CI 75% 96%). Sixteen (43%) underwent secondary surgery metastases, R0 resection 13 cases (35%). At median follow-up 17.7 months, progression-free survival 11.3 months (95% 9.7–12.9 months). After amendment, most common adverse events during induction neutropenia (48%; neutropenia: 5%), (35%), asthenia (27%), stomatitis (14%), skin toxic effect (14%). One treatment-related death registered. Conclusions Adding feasible decreasing irinotecan reduce risk diarrhoea. Activity resectability metastases among Ras–BRAF are promising.