FOLFOXIRI/Panitumumab No Better Than FOLFOX/Panitumumab for Colorectal Cancer

Standard first-line chemotherapy for metastatic colorectal cancer consists of modified FOLFOX or FOLFIRI combined with bevacizumab or an epidermal growth factor receptor (EGFR)–targeted agent in patients with left-sided primary tumors that are RAS wild type and lack BRAF V600E mutations. Initial treatment with the three-drug regimen FOLFOXIRI plus bevacizumab has been shown to enhance response and survival over two-drug chemotherapy (J Clin Oncol 2020; 38:3314).

Investigators in Italy performed a randomized, phase 3 trial comparing two-drug mFOLFOX/panitumumab therapy to three-drug mFOLFOXIRI/panitumumab therapy in patients with advanced RAS and BRAF wild-type colorectal cancer. Of 435 patients, median age was 59 years, 4% had received prior adjuvant therapy, 47% had the primary tumor resected, and 88% had left-sided primary tumors.

At a median follow up of 26.5 months, there was no difference in any treatment outcome between the three- versus two-drug regimens, including the primary endpoint of objective response rate (73%–76%; odds ratio, 0.87; P=0.526), progression-free survival (median, 12.7 and 12.3 months; hazard ratio, 0.88; P=0.277), and achievement of eventual R0 resection of metastatic disease (25% and 29%; OR, 0.81; P=0.317). Among patients with left-sided primary tumors, there was no difference in response with two-drug versus three-drug therapy (OR, 1.07). mFOLFOXIRI was more toxic, with higher rates of grade 3/4 neutropenia (32% vs. 20%), diarrhea (23% vs. 7%), and rash (29% vs. 19%), and with more treatment-related deaths (3 vs. none).