CAIRO5 Trial: FOLFOX/FOLFIRI Plus Bevacizumab Shows Efficacy in Unresectable Colorectal Liver Metastases
Key Insights
The CAIRO5 trial evaluated optimal systemic treatment for patients with unresectable colorectal liver-only metastases (CRLM).
No significant difference in overall survival was observed between FOLFOXIRI (search)-bevacizumab and FOLFOX (search)/FOLFIRI (search)-bevacizumab, regardless of RAS/BRAFV600E (search) status or tumor location.
Complete local treatment, including salvage options for early recurrence, was associated with the longest overall survival in CRLM patients.
The phase 3 CAIRO5 trial, conducted across 47 centers in the Netherlands and Belgium, provides insights into the optimal first-line systemic treatment for patients with initially unresectable colorectal liver metastases (CRLM). The study, a multicenter randomized clinical trial involving 530 patients, investigated the efficacy of different chemotherapy regimens combined with targeted therapies. The findings, published in JAMA Oncology, suggest that FOLFOX (search)/FOLFIRI (search) plus bevacizumab remains a viable option irrespective of RAS/ BRAFV600E (search) variant status and tumor sidedness.
Study Design and Key Findings
The CAIRO5 trial randomized patients with RAS/ BRAF V600E-variant and/or right-sided tumors to either FOLFOX (search)/FOLFIRI (search)-bevacizumab (group 1) or FOLFOXIRI (search)-bevacizumab (group 2). Patients with RAS/ BRAF V600E wild-type, left-sided tumors were randomized to FOLFOX/FOLFIRI-bevacizumab (group 3) or FOLFOX/FOLFIRI-panitumumab (group 4). The primary endpoint was progression-free survival, while overall survival (OS) was analyzed as a secondary outcome.
The median OS in group 1 was 23.6 months (95% CI, 20.1-27.5) versus 24.1 months (95% CI, 21.0-30.9) in group 2 (HR, 0.90; 95% CI, 0.70-1.17; P = .44). In groups 3 and 4, the median OS was 39.9 months (95% CI, 30.7-44.6) and 38.3 months (95% CI, 35.3-51.3), respectively (HR, 0.95; 95% CI, 0.68-1.32; P = .75). These results indicate no statistically significant difference in overall survival between the treatment arms within each subgroup.
Impact of Local Treatment and Adjuvant Chemotherapy
The study also assessed the impact of local treatment strategies on overall survival. Patients who underwent complete local liver treatment with salvage local treatment in case of early recurrence (≤6 months) had the longest OS (64.3 months; 95% CI, 57.6 to not reached), followed by those with salvage local treatment options after early recurrence (58.9 months; 95% CI, 47.3 to not reached). Patients without salvage local treatment after early recurrence had a median OS of 30.5 months (95% CI, 24.4-33.4), while those with incomplete local treatment had a median OS of 28.7 months (95% CI, 25.9-38.3). Patients with continued unresectability had the worst OS (18.3 months; 95% CI, 15.7-20.0).
Furthermore, the study found that adjuvant chemotherapy (ACT) after complete local treatment was associated with longer OS (HR, 0.66; 95% CI, 0.44-0.98) and relapse-free survival (HR, 0.65; 95% CI, 0.48-0.88) and less early recurrence without salvage local treatment (odds ratio, 0.46; 95% CI, 0.25-0.85) after confounder adjustment.
Clinical Implications
The CAIRO5 trial supports the use of FOLFOX (search)/FOLFIRI (search)-bevacizumab for patients with initially unresectable CRLM, regardless of RAS/ BRAFV600E (search) status and tumor sidedness. The findings emphasize the importance of complete local liver treatment, including salvage strategies for early recurrence, to maximize overall survival. The potential benefit of adjuvant chemotherapy after complete local treatment warrants consideration in these patients.