Genetic biomarker test identifying melanoma cases that are responsive to vemurafenib when given in combination with immunotherapy versus those that are unresponsive.
- Identifies patients who would benefit from combination treatment of BRAF kinase inhibitor, vemurafenib, and immunotherapy.
- Screening reduces the application of ineffective treatments.
Over 132,000 cases of melanoma are diagnosed annually, and over 60% of melanomas express a mutation in the BRAF signaling pathway that leads to uncontrolled cell growth. In cases with the mutation, late stage melanoma patients are administered vemurafenib, however 40% of those patients develop resistance to the drug. These patients are treated with immunotherapies, but only a portion of that subset responds to the immunotherapy. Although immunotherapies can be effective, they have significant side effects with high toxicity and increased resistance, particularly if the tumors are unresponsive. There is currently no method to identify melanoma cases that will or will not respond to combination vemurafenib and immunotherapy.
The most common mutation in melanoma is BRAFV600E, a component in the MAPK signaling pathway that leads to excessive cell growth. One of the leading drugs to treat patients with melanoma with the BRAFV600E mutation is vemurafenib. Unfortunately, many tumors develop resistance to the drug. In these cases an immunotherapy is often co-administered to stimulate the immune system to fight the tumor. Dr. Pollack and colleagues have found that the zygosity of the V600E mutation is predictive of whether tumors respond to vermurafenib and immunotherapy combination treatment. Using well-established melanoma positive or negative cell lines, they determined that cells homozygous for the BRAFV600Emutation are more likely to respond to immunotherapy compared to cells heterozygous for BRAFV600E. This technology could serve as a companion diagnostic for combination kinase inhibitor and immunotherapy, thereby reducing ineffective treatment. Ongoing clinical trials for such combination therapies are underway and could benefit from this type of testing to improve clinical trial design.
- In vitro melanoma cell culture lines show that homozygous BRAFV600E expression respond to immunotherapy.
- Work to replicate these results using patient samples is underway.