FOLFOXIRI Plus Panitumumab for Left-sided RAS-wild-type Metastatic Colorectal Cancer

Colorectal cancer (CRC) can be effectively treated with fluoropyrimidine chemotherapy doublets. The triplet chemotherapy program, FOLFOXIRI, is more effective than a doublet in randomized trials. We combined this triplet with the anti-epidermal growth factor receptor (EGFR) antibody, panitumumab, as first-line therapy in the appropriately targeted population: left-sided, RAS wild-type metastatic CRC.

A multicenter trial was conducted with the AGICC (Academic GI Cancer Consortium) group. Patients with stage IV or unresectable, left-sided, Rat Sarcoma Virus oncogene (RAS) wild-type CRC were eligible if they had measurable disease, adequate organ function, and Perfromance Status (PS) 0-1. Consented patients were treated with modified FOLFOXIRI and panitumumab every 2 weeks until progression or toxicity. CT scans were performed every 8 weeks. The primary endpoint was response rate by Response Evaluation Criteria in Solid Tumors (RECiST) v1.1, with an expectation of an RR ≥85%.

Twenty-nine patients were enrolled and 27 were treated. A total of 430 cycles were given, including 7 patients with the maximum of 24 cycles (median 18, range 3-24). Best response included 2 CR, 18 PR, and 6 SD (RR 74%). One patient progressed at the time of first assessment. Grade 3+ toxicity included neutropenia, diarrhea, rash, hypomagnesemia, and hypokalemia, similar to prior reports. No patient had grade 5 toxicity. Median progression-free survival (PFS) was 17.0 months, and overall survival was not reached but exceeded 36 months.

In this small US multicenter study, utilizing FOLFOXIRI with an anti-EGFR antibody for appropriately selected patients, we note that the response rates and PFS values are among the highest reported in stage IV colon cancer.