SAN FRANCISCO, CA USA (UroToday.com) - Nivolumab is a monoclonal antibody targeting PDL1, inducing immune-mediated anti-tumorigenesis.
Nivolumab has demonstrated dramatic and durable responses in the treatment of a wide variety of malignancies including renal cell carcinoma (RCC). Dr. David F. McDermott discussed ways in which to identify patients most likely to respond to PDL1 inhibition and also ways in which to improve response to PDL1 inhibitory therapy, particularly via combination with other immunotherapies or targeted therapies.
Dr. McDermott discussed studies aimed at identifying likely responders to PDL1 inhibition. Staining for PDL1 expression alone has not been shown to reliably predict response to nivolumab, as patients whose tumors are PDL1-negative may also exhibit a response to the drug. This lack of correlation between expression and response may be due to multiple factors, including tumor heterogeneity or increased PDL1 expression in the tumor microenvironment. Tumor heterogeneity contributes to the difficulty with good biomarker identification. As an example, he referenced a study presented at this conference which demonstrated differential PDL1 expression between primary and metastatic RCC sites.
He proceeded to address the question of whether patients with non-clear cell histology should be included in trials for nivolumab. Expression of PDL1 has been found in a small subset of patients with non-clear cell histology, and, thus, Dr. McDermott concluded that these patients should be considered for inclusion in nivolumab trials.
He followed with a discussion of the role of combination therapy in generating response to nivolumab in patients who otherwise would not respond. In a study examining the combination of nivolumab with ipilimumab (a CTLA4 inhibitor) in melanoma, significant declines in tumor size, with a durable response, were seen in a larger proportion of patients with PDL1-negative tumors than would be expected with nivolumab therapy alone. Multiple phase I trials are underway examining combination therapy with nivolumab at this time, and Dr. McDermott stated that he envisioned many of these immunotherapies and combination regimens over the next couple of years will become approved for use in several different types of solid tumors.
Despite this, he warned that the use of these immunotherapies in unselected patients would result in a high number of patients requiring salvage therapies, given the majority of tumors are not inflamed, and thus not likely to respond well to immunotherapy. Research into inducing antitumor activity is underway through such avenues as radiation therapy to tumor sites or the use of vaccines. He concluded by again emphasizing the importance of identifying patients who are most likely to benefit from this immunotherapy.
Highlights of a presentation by David F. McDermott, MD at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
The Dana-Farber Cancer Institute, Boston, MA USA