FROM THE 2017 GENITOURINARY CANCERS SYMPOSIUM
ORLANDO (FRONTLINE MEDICAL NEWS) – Some people with advanced kidney cancer who respond to immune checkpoint inhibitor therapy and subsequently stop because of immune-related adverse events may continue to see a clinical benefit for 6 months or longer, a retrospective, multicenter study reveals.
In fact, investigators labeled 42% of 19 patients with metastatic renal cell carcinoma (mRCC) “durable responders” to checkpoint inhibitor blockade. “What we’ve demonstrated is that, despite patients stopping their treatment, there is a subset who continue to have disease in check and controlled despite [their] not being on any therapy,” Rana R. McKay, MD , of the University of California, San Diego, said.
“Our subset was small, only 19 patients, so the next step is to validate our findings in larger study, and actually conduct a prospective trial to assess if discontinuation of therapy is worthwhile to investigate in this population,” Dr. McKay said during a press briefing prior to the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
PD-1/PDL-1 inhibitors demonstrate efficacy against an expanding list of malignancies, Dr. McKay said. The current standard is to administer these agents on a continuous basis until cancer progression or toxicity occurs. However, the study raises the possibility of intentionally discontinuing their use in some patients in the future, primarily because PD-1/PD-L1 inhibitors are associated with a wide range of side effects. Most concerning are immune-related adverse events “which are thought to be due to immune system activation,” she said.
“These drugs work to reinvigorate the immune response, and one of the unintended consequences is … they may also elicit an autoimmune response against one or more organs in the body,” said Sumanta Pal, MD , of City of Hope Medical Center in Duarte, Calif. and moderator of the press briefing.
“There was a wide spectrum of adverse events affecting different organ systems,” Dr. McKay said, “including pneumonitis, myositis, nephritis, hepatitis, pericarditis, and myocarditis, just to name a few.” A total of 84% of patients required steroids to treat immune-related adverse events, 11% needed additional immunosuppressant agents to treat their symptoms, and 53% have ongoing toxicity.
“If a patient has immune-related side effects, the impact can be serious,” Dr. Pal said. “This [study] certainly supports the premise that those individuals who experience immune related side effects could have a tangible benefit from the drug nonetheless.”
Median patient age was 68 years, 74% were male and 26% had aggressive disease. In the durable responders group, the median time on treatment was 11 months and median time off treatment was 20 months. In contrast, the patients whose cancer worsened immediately after therapy cessation were treated a median 4 months and were off treatment a median of only 2 months. A total of 63% received either PD-1 or PD-L1 monotherapy and the remainder received one of these inhibitors in combination with other systemic therapies.
Prospective studies are warranted to determine approaches to customize immunotherapy based on response, Dr. McKay said. A phase II study is planned to assess optimized management of nivolumab therapy based on response in patients with mRCC, she added
