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Cornelis JA Punt, MD, PhD, reviews Bevacizumab Plus Triplet or Double Chemo in Unresectable CRC Liver Metastases

Cornelis JA 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.

On American Society of Clinical Oncology (ASCO) 2022 Annual MeetingCancer Network® spoke with Cornelis JA Punt, MD, PhD, professor of cancer care and quality of life and oncology at Amsterdam University Medical Centers in the Netherlands, about the phase 3 CAIRO5 study (NCT02162563) that investigated bevacizumab (Avastin) plus either triplet or doublet chemotherapy in patients with initial inoperable colorectal cancer liver metastases and right side and/or BRACE/BRAF V600E – mutant primary disease. Chemotherapy regimens used included the triplet of folic acid, fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI), or doublets of the same regimen minus either oxaliplatin (FOLFIRI) or irinotecan (FOLFOX).


Patients who have colon cancer with liver metastases can be divided into 3 groups: patients who have initial resectable metastasis who should receive local treatment; patients who are initially inoperable [disease] but potentially resectable liver metastasis after decompensation with systemic treatments and who should therefore receive systemic induction therapy; and patients who have permanent unresectable metastases who are candidates for palliative systemic therapy. The problem in these 3 groups is that there is no international consensus on the criteria for resectability or unresectability. Second, there is also no consensus on the optimal systemic induction regimen. There is a lot of data from retrospective studies and subgroups [analyses of patients with] liver metastases and also some prospective studies only on liver metastases. 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 are no long-term follow-up data on any local treatments. Certainly, [available] studies are heterogeneous in design, study populations and use of RACE and BRAF mutational status.

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We chose progression-free survival as the primary endpoint [of CAIRO5] and median progression-free survival in the doublet chemotherapy plus bevacizumab arm was 9.0 months compared with 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 is a lot of data on triplet vs double chemotherapy and we confirmed with this data that there is more toxicity with triplet chemotherapy [regimen]mainly neutropenia and diarrhoea, 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 by the Dutch Colorectal Cancer Group. J Clin Oncol. 2022;40(suppl 17):LBA3506. doi:10.1200/JCO.2022.40.17_suppl.LBA3506

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