Background: The triplet-agent (5-fluorouracil/leucovorin, oxaliplatin, and irinotecan; FOLFOXIRI) combined with an anti-epidermal growth factor receptor antibody as a first-line treatment of metastatic colorectal cancer (mCRC) has shown promising results in Western trials. This phase Ib study assessed the safety of FOLFOXIRI plus cetuximab in Japanese patients with RAS wild-type mCRC.
Methods: Patients with previously untreated RAS wild-type mCRC received weekly cetuximab (400 mg/m2 at week 1 and subsequently 250 mg/m2) plus FOLFOXIRI that consisted of irinotecan (100, 120, and 150 mg/m2 defined as dose levels 0, 1, and 2), followed by oxaliplatin 85 mg/m2 and l-leucovorin 200 mg/m2 and then 5-fluorouracil 2400 mg/m2. The dose level of irinotecan was escalated starting at dose level 1 in a 3 + 3 manner. The primary endpoint was to determine the maximum-tolerated dose (MTD) and the recommended phase-2 dose (RP2D). Secondary endpoints included safety, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).
Results: Nine patients were enrolled. The MTD was not reached at dose level 2 and the RP2D was 150 mg/m2 irinotecan. The most frequent grade 3/4 adverse events were neutropenia (44%), fatigue (11%), paronychia (22%), and acneiform rash (11%). No dose-limiting toxicities occurred in any of the enrolled patients. No treatment-related death was observed. The ORR was 89% (95% confidence interval 52-100%).
Conclusion: The safety profile of the combination of cetuximab and FOLFOXIRI was acceptable and promising anti-tumor activity was demonstrated, supporting further study in patients with RAS wild-type mCRC.
Keywords: Cetuximab; FOLFOXIRI; Metastatic colorectal cancer; RAS.