Targeting BRAF and EGFR Doubles Progression-free Survival in Colorectal Cancer
Recent successes in genetically targeted precision cancer medicines are improving outcomes in a number of cancers. Ensuring patients undergo genomic sequencing to determine if they have treatable targets is increasingly important to ensure patients receive the most appropriate personalized care.
Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.
By testing an individual’s colon cancer for specific unique biomarkers doctors can offer the most personalized treatment approach utilizing precision medicines.
Many colorectal cancers express epidermal growth factor receptor (EGFR) which is a transmembrane protein with cytoplasmic kinase activity that transduces important growth factor signaling from the extracellular milieu to the cell, and EGFR can be targeted with specific medications including Erbitux (cetixumab).
BRAF is one of several other colorectal cancer biomarker that can be targeted. The BRAF gene is known to play a part in cell growth, and mutations in BRAF are common in several types of cancer. Five to 10 percent of colorectal cancer patients carry a very specific BRAF mutation known as V600E. This mutation produces an abnormal version of the BRAF protein that stimulates cancer growth. Patients with mutant BRAF genes generally have a poorer prognosis.
Zelboraf (vemurafenib) is a novel precision cancer medicine that only works in patients whose cancer has a V600E BRAF mutation. Recent clinical trial results suggest that the addition of Zelboraf to treatment with Erbitux and Camptosar (irinotecan) in patients with metastatic colorectal cancer that have a BRAF V600E mutation can improve outcomes.
In a clinical study designed to evaluate whether Zelboraf could improve the treatment of advanced colon cancer, 99 patients were treated with standard colorectal cancer chemotherapy using Camptosar plus Erbitux with or without the Zelboraf and directly compared.
The 49 patients who received Zelboraf in addition to Erbitux and Camptosar experienced a doubling of survival time without cancer progression. The disease control rate was 67% with the addition of Zelboraf versus 22% for the two-drug combination. Overall survival was a median of 5.9 months for the two-drug combination and 9.6 months with the addition of Zelboraf. The study implies that inhibiting BRAF along with EGFR in patients with advanced colon caner may be more potent than inhibiting either of these targets alone.