Pharmacology

New results from the BEACON clinical trial offer hope for a chemotherapy-free treatment option for certain patients with colorectal cancer (CRC). Combinations of targeted therapies yielded significantly improved response rates and overall survival rates compared with traditional; chemotherapy regimens among patients with previously treated BRAF V600E–mutated metastatic CRC. This BRAF V600E mutation is found in 10% to 15% of metastatic CRC patients and is usually associated with a poor prognosis.

Chemotherapy-free treatment

The BEACON trial had three treatment arms. One group of patients received triplet therapy with three targeted agents the BRAF inhibitor encorafenib (Braftovi, Array BioPharma), the MEK inhibitor binimetinib (Mektovi, Array BioPharma); and the EGFR inhibitor monoclonal antibody cetuximab (Erbitux, Eli Lilly). Another group received doublet targeted therapy with encorafenib and cetuximab. A third (control) group received standard chemotherapy.

The new results, presented here at the World Conference on Gastrointestinal Cancer (WCGC) 2019; were from an initially unplane interim analysis. Presenter Scott Kopetz, MD, PhD, from the University of Texas MD Anderson Cancer Center, Houston, shows that the triplet therapy is associate with a remarkable 48% improvement in overall survival vs standard chemotherapy. Furthermore; progression-free survival (PFS) is improve by 62%, at 4.3 months with the triplet regimen vs 1.5 months with standard therapy.

Conference on Gastrointestinal Cancer

This improvement is reflect in a highly significant increase in the objective response rate (ORR) ;with triplet therapy, at 26%. ORR increased to 34% among patients who had previously receive just one therapy. It was only 2% with chemotherapy. Importantly, these improvements were achieved without increasing toxicity, Kopetz added.

At a press conference, Kopetz commented that he was “pleased to report that really this is the first evidence of a survival benefit with a chemotherapy-free targeted therapy regimen in a prospective biomarker-defined subgroup, in this case BRAF V600E mutations in colorectal cancer. “On the basis of this; we think it really defines a new standard of care.”

Prospective biomarker

He said that the triplet therapy has already been add to the National Comprehensive Cancer Network guidelines for the treatment of metastatic CRC; “so this is now available to our patients for treatment of this difficult disease.” However; but study coauthor Eric van Cutsem, MD, PhD, from the University Hospital Gasthuisberg; Leuven, Belgium, who is co-chair of the congress; said that European patients are not yet able to benefit from this triple therapy.

He told Medscape Medical News that the European Medicines Agency “is usually more conservative” than its US counterpart and that “the regimen is not yet approve for colorectal cancer.”Moreover, cetuximab is not available in Europe. Thus; any off-label use would have to be the doublet combination of encorafenib and binimetinib.