Optimal Chemotherapy for Colorectal Cancer Liver Metastases

Epidermal growth factor receptor (EGFR)–targeted agents plus two-drug chemotherapy (e.g., FOLFOX or FOLFIRI) are preferred for use in left-sided RAS and BRAF wild-type metastatic colorectal cancers. When bevacizumab is used, three-drug chemotherapy (e.g., FOLFOXIRI) has trended superior to two-drug chemotherapy. Hepatic resection of liver metastases improves survival, and systemic chemotherapy is used to augment local regional therapy.

The open-label CAIRO5 trial evaluated four chemotherapy regimens in patients with metastatic colorectal cancer with hepatic metastases confined to the liver but potentially resectable, contingent on a response to chemotherapy. Patients with RAS or BRAF mutant cancers or right-sided primary tumors were randomized to bevacizumab plus either FOLFOXIRI or investigator's choice of FOLFOX or FOLFIRI. Patients with left-sided and RAS and BRAF wild-type cancers were randomized to either bevacizumab or panitumumab plus investigator's choice of FOLFOX or FOLFIRI. An expert panel assessed resectability.

Of 521 patients, 62% were men, 89% presented with synchronous metastases, 31% had the primary tumor resected, 74% had left-sided primary tumors, and 6% had BRAF mutations. Median follow-up was approximately 50 months. In patients with right-sided or RAS/BRAF mutant cancers, the primary endpoint of progression-free survival (PFS) was superior with FOLFOXIRI versus two-drug chemotherapy (median, 10.6 vs. 9.0 months; hazard ratio, 0.76; P=0.032). The FOLFOXIRI arm also had significantly higher response rate (54% vs. 33%; P=0.0004) and higher rate of liver-directed therapy (57% vs. 46%; P=0.79). In patients with left-sided RAS/BRAF wild-type tumors, PFS did not differ between the panitumumab and bevacizumab arms (10.4 vs. 10.8 months; HR, 1.11; P=0.46). Response rates were higher with panitumumab (80% vs. 53%; P<0.0001), but rates of liver-directed therapy did not differ (69% and 68%).