Biomarkers for melanoma help identify patients most likely to benefit from therapy and least likely to suffer unusual or severe toxicities, and they generate increased value, says Michael V. Seiden, MD, PhD, senior vice president and chief medical officer, The U.S. Oncology Network and McKesson Specialty Health, an organization focused on provider, practice management, biopharma, and payer solutions.
Melanoma has had two revolutions in biomarker discoveries. The first was based on a key genetic finding in 2002 when it was discovered that a specific mutation in the BRAF gene, found in half of individuals with melanoma, led to changes in its associated protein and promoted tumor growth, Seiden says. BRAF is a kinase (a type of enzyme) that modifies other growth promoting proteins. Targeting this protein with a drug called a kinase inhibitor and a second drug that also prevents growth (also a kinase inhibitor) has been effective in most individuals with mutations in BRAF.
A genetic test evaluating the BRAF gene is highly predictive of which patients will experience at least temporary benefit from kinase inhibitors and therefore eliminates the cost of giving these drugs to patients who won’t benefit, Seiden says.
Presently, more attention is being focused on oncology immunotherapy, i.e., the use of the immune system to treat cancer, by using immune checkpoint inhibitors, Seiden says. Still in development, they show even greater promise than kinase inhibitors.
About half of patients with advanced melanoma will respond to immunotherapy, so it is now common for all patients with advanced disease to try these agents.
About one in five individuals with advanced melanoma have been cancer free for more than three years, with some patients having been cancer free for almost a decade, suggesting that new immuno-oncology agents might cure certain individuals with metastatic melanoma.
But Seiden says there is an urgent need to determine who will achieve maximum benefit from one immunotherapy drug and which patients will only benefit from the combination of two or more drugs (all of which are very expensive and toxic). In addition, tests that might identify the subset of patients who won’t benefit from these therapies and hence might be spared the cost and risks of therapy have yet to be developed.