Researchers at the UCLA (University of California, Los Angeles) have developed a new methodology to predict the reason behind the varied response of some patients battling advanced melanoma to the new breakthrough drug pembrolizumab (Keytruda).
The study, led by UCLA Jonsson Comprehensive Cancer Center members Drs. Paul Tumeh and Antoni Ribas, primary investigator of pembrolizumab, is the first of its kind since the FDA approved the use of Keytruda in September and could lead the way for more effective use of the drug in patients with melanoma and other cancers.
AdvertisementA protein known as PD-1 puts the immune system's brakes on, preventing T cells from attacking cancer cells. Pembrolizumab removes the brake lines, freeing up the immune system to kill cancer cells.
"We've had amazing clinical success treating patients battling advanced melanoma with pembrolizumab. The challenge is that it only works in approximately 30 percent of patients with melanoma," said Tumeh, lead author of the study and assistant professor of dermatology. "To address this challenge, we developed an approach that can select for patients that are likely to respond to this therapeutic class."
"Our job was to figure out why some patients are predisposed to respond and others are not," said Ribas, professor of hematology and oncology. "Now, with these results, researchers can develop better drug combinations that are more effective, less costly and with fewer side effects."
Over the two-year study, Tumeh and Ribas analyzed 46 patients with advanced melanoma treated with pembrolizumab who had undergone tumor biopsies before and during treatment. They analyzed biopsies of patients and classified them according to whether the patient responded or not to pembrolizumab.
In collaboration with fellow Jonsson Cancer Center member Dr. David Elashoff, adjunct professor of medicine, the information allowed them to develop an algorithm able to predict the likelihood of treatment success or failure.
Fifteen additional tumor samples were obtained from patients given pembrolizumab in Paris, France, without Ribas' team knowing what the clinical outcomes were. After applying their predictive algorithm, Tumeh correctly predicted what would happen in 13 out of the 15 patient cases.
Keytruda was the first PD-1 immunotherapy drug approved by the FDA and there are eight others currently in clinical development. Ribas and Tumeh's findings will help scientists and clinicians develop and correctly prescribe the best treatment for patients with melanoma and other cancers.
"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," said Tumeh.
The findings are reported online November 26, 2014, ahead of print in the journal Nature.
This research was supported by Stand Up to Cancer and the National Institute of Health. Additional funding was provided by the UCLA Jonsson Comprehensive Cancer Center through philanthropy and other sources.