Cornelis J. A. Punt, MD, PhD, Reviews Bevacizumab Plus Triplet or Doublet Chemo in Unresectable CRC Liver Metastases

Cornelis J. A. Punt, MD, PhD, spoke about the phase 3 CAIRO5 trial of bevacizumab plus either FOLFOXIRI or FOLFOX/FOLFIRI for patients with initially unresectable colorectal liver metastases.

At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® spoke with 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, about the phase 3 CAIRO5 trial (NCT02162563) which examined bevacizumab (Avastin) plus either triplet or doublet chemotherapy in patients with initially unresectable colorectal cancer liver metastases and right-side and/or RAS/BRAF V600E–mutant primary disease. 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).


Patients who have colorectal cancer with liver metastasis can be divided into 3 groups: patients who have initially resectable metastasis who should receive local treatments; patients who initially have unresectable [disease] but potentially resectable liver metastasis after downsizing by systemic treatments and who, therefore, should receive induction systemic treatment; and patients who have permanently unresectable metastasis who are candidates for palliative systemic treatment. The problem in these 3 groups is that there is no international consensus on the criteria for resectability or unesectability. Secondly, there’s also no consensus on the optimal induction systemic regimen. There are a lot of data from retrospective studies and subgroup [analyses of patients with] liver metastasis and also some prospective studies in liver metastases only. Most if not all of these studies are hampered by the fact that there is a lack of clear criteria for unresectabe or resectable [disease]. There is no long-term follow-up data on any local treatments. Certainly, [available] studies are heterogeneous in their design, study populations, and use of RAS and BRAF mutational status.

We selected the progression-free survival as the primary end point [of CAIRO5] and the median progression-free survival in the doublet chemotherapy plus bevacizumab arm was 9.0 months vs the triplet chemotherapy plus bevacizumab arm at 10.6 months. This had a hazard ratio of 0.77 [95% CI, 0.60-0.99] which was statistically significant with a P-value of 0.038.

There are a lot of data of triplet vs double chemotherapy and we confirmed with these data that there is more toxicity with a triplet chemotherapy [regimen], mainly neutropenia and diarrhea, but it was manageable.


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