1976 - BRAF-mutated colorectal metastases: what is the benefit of liver surgery? Results from a cohort of 91 patients.

Background

BRAF V600E-mutated colorectal liver metastases (CRLM) are associated with higher relapse rate and shorter survival time after resection as compared to BRAF wild-type CRLM. It remains unsure whether metastatic surgery has a benefit over chemotherapy alone in this setting. To address this question, we analyzed a large cohort of BRAF-mutated CRLM patients in order to evaluate the impact of liver surgery on overall survival (OS).

Methods

We retrospectively identified BRAF-mutated colorectal cancers diagnosed with liver-only metastases (n = 91) resected or not from October 1, 2003 to December 31,2017 in 24 French centers. The impact of CRLM resection on OS (primary endpoint) was analyzed by Kaplan-Meier method and Cox model. OS was defined from the time of CRLM diagnosis to death from any cause. Progression free survival (PFS) was defined from the time of first chemotherapy (even for resected patients) to first progression or death.

Results

Ninety-one patients were included: 43 (47%) with resected CRLM and 48 (53%) treated with chemotherapy only. Among resected CRLM, 34 (79%) received chemotherapy before surgery. BRAF V600E mutation was detected in 83 (91%) patients and non-V600E mutation in 8 (9%) patients. In comparison to resected CRLM, unresected CRLM were more often bilobar (76% versus 51%, p = 0.03) and greater than 5 (62% versus 34%, p = 0.02). There was no statistical difference in the other criteria especially in rates of synchronous metastases (94% versus 81%, p = 0.11). Median OS was 32.1 months for resected patients and 11.4 months for unresected patients (p < 0.0001). In univariate analysis, 4 parameters were statistically associated with poor OS: rectum primary site (p = 0.002), greater than 5 (p = 0.018), BRAF V600E mutation (p = 0.010) and no liver surgery (p < 0.0001). In multivariate analysis, liver surgery was the only variable associated with significant longer OS (hazard ratio [HR]= 0.125, CI 95%: 0.068 – 0.229, p < 0.0001) and PFS (HR = 0.173, CI 95% 0.101 – 0.296, p < 0.0001).

Conclusions

To our knowledge, this is the largest cohort of colorectal cancer with liver-only metastases harboring BRAF V600E mutation. Liver surgery extend significantly OS and therefore CRLM resectability should be assessed in BRAF-mutated colorectal cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Ploquin, Anne.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.