Colorectal cancer (CRC) is among the most frequently diagnosed malignancies, with roughly 20% of patients presenting with metastases at the time of diagnosis, and 50%-60% eventually developing metachronous metastatic lesions. Although skeletal metastases are relatively uncommon, they are often linked to increased disease burden, poorer prognosis, diminished quality of life, and substantial healthcare costs. Recently, the combination of FOLFOXIRI and bevacizumab has been established as the preferred standard of care for metastatic CRC, based on the positive outcomes of the TRIBE and TRIBE2 trials. Despite its overall efficacy, evidence regarding the performance of this regimen in patients with bone metastases is limited. We conducted a pooled analysis of the TRIBE and TRIBE2 trials, focusing specifically on individuals with bone metastases. In the overall cohort, patients with bone involvement at baseline exhibited shorter overall survival (OS; 14.0 versus 26.2 months; hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.46–2.87; P < 0.001) and progression-free survival (PFS; 6.2 versus 11.1 months; HR 1.96, 95% CI 1.42–2.69; P < 0.001) compared with those without bone lesions. No significant interaction between treatment and bone involvement was observed for PFS (P = 0.094) or OS (P = 0.38). In multivariate analysis, bone metastases remained a negative prognostic factor (HR 2.24, 95% CI 1.54–3.26; P < 0.001). Additionally, patients whose first radiological progression involved bone (including those with pre-existing bone metastases) had reduced OS compared with those who progressed at other sites (10.4 versus 13.2 months; HR 1.48, 95% CI 1.15–1.91; P = 0.002). A trend toward shorter OS (7.5 versus 11 months; HR 1.50, 95% CI 0.92–2.45; P = 0.10) was observed in patients with baseline bone metastases compared to those who developed skeletal involvement at first progression. These results confirm that bone metastases negatively affect prognosis in CRC. Importantly, our study demonstrates for the first time that the survival benefit of triplet chemotherapy combined with bevacizumab persists in this high-risk subgroup.
