Marinde J.G. Bond, PhD Candidate, on Colorectal Liver Metastases: FOLFOX/FOLFIRI, Bevacizumab, and Panitumumab

CAIRO5 is the first randomized controlled phase III trial in which the currently most effective systemic regimens were compared in defined subgroups of patients with initially unresectable colorectal cancer liver metastasis, as defined by a liver expert panel. Patients with RAS/BRAF-mutated and/or a right-sided primary tumor were randomized between dub chemotherapy and triplet chemotherapy, both plus bevacizumab. The results of this group were presented at ESCO annual meeting last June and patients with RAS/BRAF wild-type, and left-sided primary tumors were randomized between doublet chemotherapy and either bevacizumab or panitumumab. I presented the results of this group, which evaluated 230 patients. A novel aspect of this study is the Liver Expert Panel, which evaluates unresectability at baseline, according to redefined criteria, and resectability every 2 months during follow up, the Liver Expert Panel consisted of 15 liver surgeons and three abdominal radiologists. The panel procedure was as follows. The CT scans were uploaded and reviewed by one abdominal radiologist and then by three liver surgeons. If no consensus among these three liver surgeons existed, then two additional surgeons were invited and the final decision was made by majority votes. Consensus on unresectability at baseline was present in 67% and during follow up in 42%. Based on these results and the results of in-depth analysis, we can conclude that the use of a liver expert panel is feasible and allows the selection of an increased number of patients who are eligible for local treatments with curative intent. The primary endpoint was progression-free survival and the median progression-free survival in the bevacizumab of arm, 10.6 months, and in the panitumumab arm, 10.3 months. This was not significantly different, with a hazard ratio of 1.12 and the p-value of 0.44. Panitumumab was associated with more grade 3 or higher toxicity, which mainly consisted of skin toxicity and diarrhea. Panitumumab significantly increased response rate and depth of response, which, however, did not translate into an increased local treatment rate of liver metastasis. In conclusion, the median progression free survival was not different between the use of either bevacizumab or panitumumab to FOLFOX or FOLFIRI. The local treatment rate was not significantly different either despite the higher response rate and higher depth of response. Considering the results of previous anti-EGFR trials, the data and overall survival should be weighted before we can draw a final conclusion about the use of anti-EEGR therapy in patients with initially unresectable colorectal cancer liver metastasis and their-left sided and RAS/BRAF wild-type tumor.