Bone metastases are associated with worse prognosis in patients affected by metastatic colorectal cancer treated with doublet or triplet chemotherapy plus bevacizumab: a subanalysis of the TRIBE and TRIBE2 trials.

BACKGROUND

Colorectal cancer (CRC) is one of the most common cancers; ∼20% of patients have metastases at diagnosis, and 50%-60% subsequently develop metachronous metastases. Bone involvement, despite being rare, is usually associated with higher disease burden, worse prognosis, impaired quality of life, and significant health-related cost. In the last few years, following the positive results of the TRIBE and TRIBE2 trials, the association of FOLFOXIRI plus bevacizumab has become the new standard of care for metastatic CRC. Despite being highly efficacious in all subgroups, little is known about the activity of this regimen in patients with bone metastases.

PATIENTS AND METHODS

We carried out a pooled analysis of TRIBE and TRIBE2 studies focusing on patients with skeletal deposits.

RESULTS

Our analyses on the whole population showed that patients with baseline bone involvement reported 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 metastases; no significant interaction with the treatment was reported for PFS (P = 0.094) and OS (P = 0.38). Bone metastases had a negative prognostic implication in the multivariate analysis (HR 2.24, 95% CI 1.54-3.26; P < 0.001). Furthermore, patients with bone lesions at first radiological progression (including those with baseline bone metastases) had a shorter OS compared with those who progressed in other sites (10.4 versus 13.2 months; HR 1.48, 95% CI 1.15-1.91; P = 0.002). A trend toward inferior OS (7.5 versus 11 months, HR 1.50, 95% CI 0.92-2.45; P = 0.10) appeared in patients with basal skeletal deposits compared with those with bone involvement at first radiological progression.

CONCLUSIONS

Our study confirmed the negative prognostic impact of bone metastases in CRC. Furthermore, we demonstrated for the first time that the survival advantage of triplet chemotherapy plus bevacizumab is maintained even in this prognostically unfavorable subgroup.

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure CC reports consulting or advisory role for Roche, Bayer, Amgen, MSD, and Pierre Fabre; is on the speakers bureau for SERVIER and Merck; honoraria from Roche, Amgen, Bayer, SERVIER, MSD, Merck, Pierre Fabre, and Organon; research funding from Merck, Bayer, Roche, and SERVIER. DR is on the speakers bureau for MSD Oncology. SL received consulting or advisory role from Amgen, Merck Serono, Lilly, AstraZeneca, Incyte, Daiichi-Sankyo, Bristol-Myers Squibb, Servier, and MSD; is on the speakers bureau for Roche, Lilly, Bristol-Myers Squibb, Servier, Merck Serono, Pierre-Fabre, GSK, and Amgen; research funding from Amgen, Merck Serono, Bayer, Roche, Lilly, Astra Zeneca, and Bristol-Myers Squibb. AZ is on the speaker’s bureau for Amgen, Merck Serono, MSD, Bayer, Servier, and AstraZeneca. GV received accommodation reimbursement from Roche and Amgen. GM received contribution for advisory role from Eisai, Roche, MSD, and Amgen. All other authors have declared no conflicts of interest.