Cornelis J. A. Punt, MD, PhD, Discussed How CAIRO5 Results of Bevacizumab Plus Triplet Chemo for Unresectable CRC Liver Mets Reinforce Use of the Regimen

Cornelis J. A. Punt, MD, PhD, spoke about bevacizumab plus either FOLFOXIRI or FOLFOX/FOLFIRI in patients with unresectable colorectal liver metastases and right-sided or RAS/BRAF-mutant tumors and how these regimens may be used for curative-intent therapy.

Cornelis J. A. Punt, MD, PhD, full professor of Cancer Treatment and Quality of Life as well as Oncology at Amsterdam University Medical Centers in the Netherlands, spoke with CancerNetwork® at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting about success of bevacizumab (Avastin) plus triplet vs doublet chemotherapy from the phase 3 CAIRO5 trial (NCT02162563) in patients with initially unresectable colorectal liver metastases and right-sided and/or RAS/BRAF-mutant tumors. Chemotherapy regimens used included the triplet of folinic acid, fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI), or doublets of the same regimen minus either oxaliplatin (FOLFIRI) or irinotecan (FOLFOX). In addition to other outcomes he details, median progression-free survival observed in the triplet arm was 10.6 months vs 9.0 month with doublet therapy (HR, 0.77; 95% CI, 0.60-0.99; P = .038).


An important finding was that the rate of successful local treatment, which we defined as an R0 or R1 resection with or without ablation of all liver metastasis, was 37% in the control arm with doublet chemotherapy bevacizumab vs 51% in the triplet chemotherapy plus bevacizumab arm [P = .02]. That is a significant and clinically relevant difference. You don’t know in advance which patient’s metastases will become resectable. These data confirm that in this patient population, FOLFOXIRI plus bevacizumab should be the standard of care as well as in patients with liver metastasis because they have a higher chance for local treatments with curative intent.

We had a novel aspect of the study because we used a liver expert panel as opposed to the opinion of a single liver surgeon. We had all CT scans reviewed by an abdominal radiologist centrally and thereafter were reviewed by liver surgeons. When 3 liver surgeons had the same recommendation and consensus on resectability or unresectability, this advice was followed. However, when there was no consensus, 2 additional liver surgeons reviewed the CT scan and the decision was made by a majority vote. The consensus on baseline of resectability vs unresectability was 61% and at follow-up elevation was 41%. From these data, we conclude that if you use 3 to 5 liver surgeons for each individual patient, you will have more patients who will become eligible for local treatments with curative intent.


Punt CJA, Bond MJG, Bolhuis K, 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. J Clin Oncol. 2022;40(suppl 17):LBA3506. doi:10.1200/JCO.2022.40.17_suppl.LBA3506