Triplet chemotherapy beats doublet chemotherapy in colorectal cancer liver metastases

The CAIRO5 trial showed triplet chemotherapy to be superior to doublet chemotherapy in terms of efficacy in patients with initially unresectable colorectal cancer liver metastases (CRLM) and right-sided and/or RAS/BRAFV600E-mutated primary tumours, at the expense of increased but manageable toxicity. The use of a liver expert panel increased the selection of patients who received local treatment with curative intent.

Patients with initially unresectable CRLM are treated with induction systemic treatment, however there is no consensus on the criteria for resectability of CRLM and on the systemic induction regimen that should be administered to these patients. The phase 3 CAIRO5 trial (NCT02162563) installed a liver panel to confirm the unresectability (by surgery-only in one stage) of patients with initially unresectable CRLM [1]. Hereafter, those with RAS/BRAFV600E-mutated and/or right-sided primary tumours (n=294) were randomised to FOLFOX/FOLFIRI plus bevacizumab (doublet chemotherapy) or FOLFOXIRI plus bevacizumab (triplet chemotherapy). Progression-free survival (PFS) was the primary endpoint. Results were presented by Prof. Cornelis Punt (University Medical Center Utrecht, the Netherlands).

After a median follow-up of 41 months, the median PFS was significantly longer in patients who had received FOLFOXIRI than in those that had received doublet chemotherapy (10.6 vs 9.0 months; HR 0.77; P=0.038). At this point in time, the overall survival data was not yet mature. Furthermore, the subgroup analysis did not demonstrate an association between baseline unresectability status or mutation status and PFS. The overall response rate was higher in the triplet chemotherapy arm (53.5% vs 33.3%; P<0.001). However, grade ≥3 adverse events were more common in patients who underwent triplet chemotherapy than in those who underwent doublet chemotherapy (75.7% vs 59.2%; P=0.003), mostly due to an increased rate of neutropenia (38.2% vs 12.9%) and diarrhoea (19.4% vs 3.4%).

CAIRO5 is the first randomised trial to prospectively demonstrate the clinical benefit of triplet versus doublet chemotherapy in patients with initially unresectable CRLM and right-sided and/or RAS/BRAFV600E-mutated primary tumours. Prof. Punt added that the use of a liver expert panel is feasible and allows the selection of an increased number of patients who are suitable to receive local treatment with curative intent.

1. Punt CJA, et al. FOLFOXIRI + bevacizumab versus FOLFOX/FOLFIRI + bevacizumab in patients with initially unresectable colorectal liver metastases (CRLM) and right-sided and/or RAS/BRAFV600E-mutated primary tumor: Phase III CAIRO5 study of the Dutch Colorectal Cancer Group. LBA3506, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.

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Posted on 5 August, 202228 March, 2024