PD-1 inhibitor benefit possible even after discontinuation

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Persistent clinical benefit was seen among a small group of patients with metastatic renal cell carcinoma who had to discontinue therapy with the PD-1 inhibitor nivolumab (Opdivo) because of immune-related adverse events, according to a study presented at the Genitourinary Cancers Symposium in Orlando, FL.

Persistent clinical benefit was seen among a small group of patients with metastatic renal cell carcinoma (RCC) who had to discontinue therapy with the PD-1 inhibitor nivolumab (Opdivo) because of immune-related adverse events, according to the results of a study presented at a press conference ahead of the Genitourinary Cancers Symposium in Orlando, FL.

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“Responders to PD-1/PD-L1 targeted therapy can have persistent clinical benefit despite treatment discontinuation for immune-related adverse events,” researcher Rana R. McKay, MD, of University of California San Diego School of Medicine, said during the press conference.

According to Dr. McKay, PD-1/PD-L1 inhibitors are associated with a wide variety of immune-related side effects, which are thought to occur because of immune system activation. With this study, she and her colleagues examined the outcomes of patients with metastatic RCC who responded to immunotherapy treatment but had to stop therapy because of side effects. The study included 19 patients with metastatic RCC who were treated with nivolumab.

“The patients in this cohort experienced a wide spectrum of adverse events affecting differing organ systems. These included pneumonitis, myositis, nephritis, hepatitis, pericarditis, and myocarditis, just to list a few,” Dr. McKay explained.

Patients were classified as durable responders if they were free from progression for more than 6 months after treatment discontinuation. Patients were classified as immediate progressors if they progressed within 4 months of discontinuation.

Of the 19 patients, 63% were treated with nivolumab monotherapy. The overall median duration of therapy was 5.5 months. One patient had a complete response, seven patients had partial response, and one had stable disease.

Next: After patients stopped treatment, 42% were considered durable responders

After patients stopped treatment, 42% were considered durable responders. These patients had a median time off treatment prior to discontinuation of 11 months, with a median time off treatment of 20 months. Sixteen percent of patients were immediate progressors and the remaining patients were classified as “other,” progressing somewhere between 4 and 6 months after discontinuation.

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“Prospective studies are warranted to investigate approaches to customize immunotherapy based on response. This will be done in the phase II study of Optimized Management of Nivolumab based on Response in patients with advanced RCC (OMNIVORE),” Dr. McKay said.

Commenting on the results of the study, press conference moderator Sumanta Pal, MD, said, “There has been a tidal wave of new immune therapies developed for cancer in the last several years and perhaps the most prominent class of these drugs is PD-1/PD-L1 inhibitors. These drugs work to reinvigorate the immune response and one of the unintended consequences is that they may elicit an autoimmune response against one or multiple organs in the body.…If the patient has an immune-related side effect, the impact may be serious, but there is also the possibility that they can have a protracted benefit from the drug in terms of their cancer remaining dormant or shrinking for protracted period of time.”

“Further research is needed to validate this phenomenon,” added Dr. Pal, of City of Hope, Duarte, CA.

Dr. McKay’s institution has received funding from Bayer and Pfizer, and several of her co-authors have a financial or other relationship with Bristol-Myers Squibb and/or other pharmaceutical companies. In addition, several of her co-author’s institutions have received research funding from Bristol-Myers Squibb and/or other pharmaceutical companies.