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Who Will Respond to PD-1 Inhibition? Study Provides Clues

March 24, 2015, by NCI Staff

Specific DNA changes in a tumor may help determine which patients are most likely to respond to treatment with PD-1 inhibitors, according to findings from a new study by researchers at Memorial Sloan Kettering Cancer Center.

The FDA has approved two PD-1 inhibitors: nivolumab (Opvido) and pembrolizumab (Keytruda). Both are part of a class of immunotherapy drugs known as checkpoint inhibitors.

Patient responses to checkpoint inhibitors have been highly variable, with some patients experiencing long-lasting tumor responses, but others having only short-lived tumor shrinkage or disease stabilization or no response at all.

The study, published March 12 in Science, showed that patients with lung cancer whose tumor cells had high levels of DNA damage—as measured by the number of genetic mutations that resulted in a changed protein—were more likely to experience tumor shrinkage and had longer progression-free survival when treated with pembrolizumab than patients whose tumors had modest to little genetic damage.

The patients who had the strongest responses were those whose tumors had genetic mutations commonly associated with tobacco smoking, lead author Naiyer Rizvi, M.D., and his colleagues reported. Treatment efficacy also correlated with a high number of proteins expressed only on tumors, called neoantigens.

“This is an important first step toward being able to predict who will respond to PD-1 inhibitors and could be a new way to think about precision medicine based on the sequencing of tumor DNA,” Dr. Rizvi said in a news release.

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