Investigational agent may boost immune system of kidney Ca patients

June 27, 2012

Two clinical trials testing experimental drugs aimed at restoring the immune system’s ability to spot and attack cancer have shown promising early results in patients with kidney cancer, as well as those with advanced non-small cell lung cancer and melanoma.

Two clinical trials testing experimental drugs aimed at restoring the immune system’s ability to spot and attack cancer have shown promising early results in patients with kidney cancer, as well as those with advanced non-small cell lung cancer and melanoma.

More than 500 patients were treated in the studies of two drugs that target the same immune-suppressive pathway, and the studies’ authors say there is enough evidence to support wider testing in larger groups of patients. Results of the phase I clinical trials were presented at the American Society of Clinical Oncology annual meeting in Chicago and published online in the New England Journal of Medicine (June 2, 2012).

"Based on the positive response rates to these drugs and longevity of many of these responses, we believe that new clinical trials should move forward," said co-author Suzanne Topalian, MD, of Johns Hopkins Kimmel Cancer Center, Baltimore.

Preliminary analysis shows that, among responding patients who were followed for more than 1 year, responses were maintained for more than 1 year in two-thirds of those treated in one trial and in half of those in the other trial.

The immune-based therapies tested in the two clinical trials aim not to kill cancer cells directly, but to block a pathway that shields tumor cells from immune system components able and poised to fight cancer.

The pathway includes two proteins called programmed death-1 (PD-1), expressed on the surface of immune cells, and programmed death ligand-1 (PD-L1), expressed on cancer cells. When PD-1 and PD-L1 join together, they form a biochemical "shield" protecting tumor cells from being destroyed by the immune system.

The PD-1 blocking drug was tested in 296 patients with various advanced cancers who had not responded to standard therapies. Of those patients receiving the anti-PD-1 therapy, 240 who started treatment by July 2011 were analyzed for tumor response. Significant tumor shrinkage was seen in nine of 33 kidney cancer patients (27%).

In this trial, some patients experienced stable disease for 6 months or more, including 27% of kidney cancer patients. The investigators say that additional clinical studies will be needed to determine the drug’s potential impact on survival.

"The positive results from both drugs give us a good indication that the PD-L1/PD-1 pathway is an important target for cancer therapy," Dr. Topalian said.

Funding for the study was provided by Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Dr. Topalian is a consultant/adviser for Amplimmune and Bristol-Myers Squibb and has received research funding from Bristol-Myers Squibb. Several of her co-authors are consultant/advisers; hold employment/leadership positions; own stock; receive honoraria; and/or receive research funding from Bristol-Myers Squibb.

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