Last September, the Food and Drug Administration (FDA) approved pembrolizumab, which was found to be affective against melanoma, a deadly form of skin cancer. Sadly, not all melanoma patients benefit from the treatment and UCLA Jonsson Comprehensive Cancer Center investigators have determined a method that will predict which patients will respond to the drug. Their research should lead to more effective treatment of melanoma patients. The findings of the two year study were published online on November 26 in the journal Nature.
Study leaders Paul Tumeh, MD and Antoni Ribas, MD, PhD note that their study could pave the way to not only patients with melanoma but also other forms of cancers. It is known that a protein, PD-1, suppresses the immune system; thus, preventing T cells from attacking cancer cells. However, pembrolizumab prevents this suppression and results in the immune system attacking and killing the malignant cells.
Dr. Tumeh, an assistant professor of dermatology, explained, “We’ve had amazing clinical success treating patients battling advanced melanoma with pembrolizumab. The challenge is that it only works in approximately 30% of patients with melanoma. To address this challenge, we developed an approach that can select for patients that are likely to respond to this therapeutic class.” Dr. Ribas, a professor of hematology and oncology, added, “Our job was to figure out why some patients are predisposed to respond and others are not. Now, with these results, researchers can develop better drug combinations that are more effective, less costly and with fewer side effects.”
The researchers evaluated 46 patients with advanced melanoma treated with pembrolizumab who had undergone biopsies of their tumors both before and during treatment. They reviewed the biopsies and classified them according to whether the patient responded to pembrolizumab. Together with their colleague, David Elashoff, PhD, an adjunct professor of medicine, they used the data to develop an algorithm that could predict the likelihood of treatment success or failure.
In addition to the 46 patients, 15 additional tumor biopsies were done on patients given pembrolizumab in Paris, France, without the UCLA researchers knowing what the clinical outcomes were. After applying their predictive algorithm, Dr. Tumeh correctly predicted the outcome of 13 out of the 15 patients. Drs. Tumeh and Ribas note that before pembrolizumab, another melanoma drug, keytruda was the first PD-1 immunotherapy drug approved by the FDA and there are eight other medications currently in clinical development. They are of the opinion that the study findings will aid researchers and clinicians develop and correctly prescribe the best treatment for patients with melanoma and other cancers. Dr. Tumeh said, “The next big step is to classify the different types of patients that do not respond to treatments so we could modulate the drug to target their tumors.”