Retrospective analysis of management of BRAF V600E mutated colorectal cancer in a single institution

BRAF V600E mutation is estimated to be present in 5-20% of all new diagnosis of metastasic colorectal cancer, in which allocates a poor prognosis, with a median overall survival (OS) of 6-8 months in several retrospective studies in the literature. Encorafenib-cetuximab takes a stance in second-line treatment of this population, increasing their overall survival up to 9,3 months accoding of the BEACON study, after progression to a front line.

We realized a retrospective, unicentric study, from January 2020 to December 2022, of patients with BRAF V600E-mutated metastasic colorectal cancer and the sequence of their treatment. Demographic data were collected from their medical record: type of chemoteraphy, adverse events, end of treatment and time of death. Demographic and survival analysis were realized with IBM SPSS Statistic 27.0.1.0.

Fifteen patients were included in our study, 8 women and 7 men, with a median age of 63 years-old. Primary tumor was right-side in 3 patients and left-side in 12 patients, Apart from BRAF V600 mutation, 20% of patients present TP53 mutation, and 33,3% of them high microsatellite instability. At diagnosis, 80% patients were at stage IV (26% peritoneal metastases, 26% liver metastases and 13% lung metastases). Front-line treatment was a triplet combination chemoteraphy (oxaliplatin, 5-fluorouracil or capecitabine and bevacizumab) in 40% of patients, and doublet combination (without bevacizumab) in 46% of them, with a median progression-free survival (PFS) of 8,2 months. The combination was well tolerated with neuropathy grade (G) 2 as the most frequent adverse event (AE). Second-line treatment choice, in 53,3% of patients were encorafenib and cetuximab, 5-fluorouracil-irinotecan-bevacizumab (FOLFIRI-bevacizumab) in 33,3%. PFS of patients treated with encorafenib-cetuxumab was 9,9 months. This option was well tolerated, with rash G2 in 20% of patients. Nine patients received a third-line treatment, 33,3 % of them with encorafenib-cetuximab, 22% of them with FOLFIRI-bevacizumab, and the rest of them with FOLFIRI. PFS of ptients treated with encorafenib-cetuximab in this period was 10,4 months. At the end of follow-up of this study (December 2022) 9 patients were still alive and under treatment and 6 of them were already dead.

Our study emphasizes the poor prognosis of BRAF V600E-mutated metastasic colorrectal cancer, In our population, similar as the one in the BEACON study, the combination of encorafenib-cetuximab stands out as a well-tolerated option in second line, with a PFS of 9,9 months. Of note, in our experience encorafenib-cetuximab could also be a remarkable option in third-line setting, with a PFS of 10,4 months.

The authors.

Has not received any funding.

M. Valladares-Ayerbes: Advisory / Consultancy: merck, amgen, bayer, servier; Research grant / Funding (institution): roche; Travel / Accommodation / Expenses: merck, amgen, roche, bayer, servier. All other authors have declared no conflicts of interest.