Triplet targeted combination therapy appears to induce potent BRAF kinase signalling inhibition in patients with BRAFV600E-mutated metastatic colorectal cancer.
Result from the BEACON study have shown for the first time that a combination of three targeted agents—encorafenib, cetuximab and binimetinib—leads to improved outcomes for patients with metastatic colorectal cancer (CRC) positive for the BRAF V600E mutation who have failed first-line treatment. In updated results based on 444 patients randomised in the phase III study (Abstract LBA32) presented yesterday, the triplet combination was associated with substantially superior median overall survival (9.0 months versus 8.4 months; hazard ratio 0.79, 95% confidence interval 0.59–1.06) and objective response rate (26% versus 20%) compared with the doublet (encorafenib plus cetuximab). Prof. Andrés Cervantes from Hospital Clínico Universitario de Valencia, Valencia, Spain comments, “The triplet combination targets both upstream and downstream signalling of BRAF. Treatment appears to provide potent blockade of BRAF kinase signalling and leads to an improvement in survival not previously seen in the second-line setting in these patients.”
“BEACON is a practice-changing study that shows the benefit of a treatment regimen that, crucially, avoids the use of chemotherapy,” says Prof. Andrés Cervantes from Hospital Clínico Universitario de Valencia, Valencia, Spain.
In advanced CRC and other cancers, BRAF mutations are associated with poor prognosis, but new treatment options and specific genomic testing may have a significant impact on patients. “Genomic testing for BRAF V600E mutations can now be used as an important predictive factor in patients with advanced CRC, as we have potential treatment combinations that specifically target BRAFV600E-mutated tumours,” comments Cervantes .“While this combination has thus far only been tested in the second-line setting, it deserves exploration as a first-line treatment.”
Further positive news for patients with BRAF V600E-mutated CRC stem from a second study presented at the Congress revealing that surgery for liver metastases in this setting may be linked to improved outcomes. In the retrospective series of 91 patients with BRAF V600E-mutated CRC and liver-only metastases, multivariate analysis found that surgery was associated with significantly longer overall survival and progression-free survival than a chemotherapy-only strategy (Abstract 564P) “The role of metastatic liver surgery in patients with BRAF V600E-mutated CRC is contentious because there is a lack of supporting data,” says Cervantes. “From previous studies, surgery was demonstrated to be beneficial in BRAF-wild type CRC tumours. It now appears that surgery of resectable liver metastases could also be the goal for fit patients with BRAF V600E-mutated tumours.”
ESMO Congress 2019 abstracts:
- LBA32 – Encorafenib plus cetuximab with or without binimetinib for BRAF V600E–mutant metastatic colorectal cancer: Expanded results from a randomized, 3-arm, phase III study vs the choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC)
- 564P – BRAF-mutated colorectal metastases: What is the benefit of liver surgery? Results from a cohort of 91 patients