In research to be presented at the AACR Annual Meeting 2014, investigators at Dana-Farber Cancer Institute report a promising way of predicting which patients with non-small cell lung cancer (NSCLC) are most likely to benefit from a drug that frees up an immune system attack on tumor cells.
Results from an ongoing phase 1 clinical trial indicate that patients whose tumor cells carry high levels of the protein PD-L1 fare significantly better than other patients after treatment with the drug MK-3475. Six months after starting treatment, 41 percent of patients with high PD-L1 levels in their tumors had no worsening of their disease, compared with 17 percent of those with low PD-L1 levels. Also, 72 percent of patients whose tumors had high levels of PD-L1 were alive at the time the results were gathered, compared with 53 percent of those whose tumors had low levels of PD-L1.
"Outside of selected populations, patients with NSCLC have few good treatment options and there is a real need for something better than we currently have," said Leena Gandhi, MD, PhD, a thoracic oncologist at Dana-Farber, who helped lead the study. "The responses we have seen among patients whose tumors express high levels of PD-L1 appear to be quite durable, which is extremely exciting.
"Immune cells called T cells are naturally capable of destroying cancer cells," Gandhi explained. "But some cancer cells are able to prevent T cells from attacking them by activating the T cells' 'brakes.' One way they do this is via the PD-L1 protein on their surface, which attaches to the PD-1 protein on T cells. MK-3475 disables this brake by blocking PD-1, preventing it from attaching to PD-L1."
Using data on 146 patients enrolled in the trial, Gandhi and her colleagues found that PD-L1 levels greater than 50 percent, as measured by immunohistochemistry, served as the best cutoff point for defining whether a tumor is likely to respond to therapy with MK-3475. Of the 41 patients with high pretreatment tumor PD-L1 levels, 37 percent responded to MK-3475, compared with 11 percent for those with low pretreatment tumor PD-L1 levels.
"These data strongly suggest that high levels of tumor PD-L1 may be a good biomarker for determining which patients with NSCLC are most likely to benefit from treatment with MK-3475," said Gandhi.
This study was funded by Merck. Gandhi declares no conflicts of interest.