Some benefit derived from immunotherapy for kidney cancer despite treatment discontinuation
Patients with metastatic renal cell carcinoma (RCC) who discontinue immunotherapy due to adverse events can still derive clinical benefit, according to a small study presented at the American Society of Clinical Oncology (ASCO) 2017 Genitourinary Cancers Symposium (GU 2017) in Orlando, Florida, US.
“Responders to PD-1/PD-L1 targeted therapy can have persistent clinical benefit despite treatment discontinuation for immune-related adverse events,” said study lead author Dr Rana McKay, an Assistant Professor of Medicine at the University of California San Diego School of Medicine, California, US.
Forty-two percent of patients were considered durable responders, remaining off therapy for more than 6 months, while 16 percent were immediate progressors (<4 months off treatment). [ASCO GU 2017, abstract 467]
Among durable responders, median time on treatment prior to discontinuation was 11 months and median time off treatment was 20 months, while among immediate progressors, median time on and off treatment was 4 and 2 months, respectively. At time of analysis, 75 percent of durable responders were free from progression.
Participants in this retrospective analysis were individuals with metastatic RCC (n=19, median age 68 years, 74 percent male) treated with PD-1/PD-L1 targeted therapy who discontinued treatment due to immune-related adverse events. The patients were categorized based on their time off treatment after discontinuation – durable responders, immediate progressors, and others (4–6 months off treatment).
A majority of patients (58 percent) had received PD-1 monotherapy and median time on immunotherapy was 5.5 months. Fifty-eight percent of patients had received prior systemic therapy and 95 percent had clear cell histology.
“The current standard is to administer these treatments on a continuous basis until progression or toxicity,” said McKay. “PD-1/PD-L1 inhibitors are associated with a spectrum of side effects termed immune-related adverse events, which are thought to be due to immune system activation.”
Among the adverse events experienced by the subjects were arthritis, uveitis, myositis, blepharitis, hepatitis, pericarditis, pneumonitis, and nephritis. Eighty-four percent and 11 percent of patients required steroids and additional immunosuppressive agents, respectively, to treat their immune-related adverse events.
“One of the unintended consequences [of PD-1/PD-L1 inhibitors] is that besides eliciting an immune response against cancer, they may also potentially elicit an autoimmune response against one or multiple organs in the body,” said Dr Sumanta Pal who represented ASCO as moderator of the GU 2017 presscast.
“As [McKay] has nicely summarized, if the patient has immune-related side effects, the impact can be serious, but there is also the possibility that they could have a protracted benefit from the drug in terms of their cancer remaining dormant or shrinking for a protracted period of time. This supports the premise that those individuals who do experience immune-related side effects could have a tangible benefit from the drug, nonetheless,” said Pal.
Due to the small size of the study, larger, prospective studies are needed to “investigate approaches to customize immunotherapy based on response”, said McKay, stating that this will be carried out in the phase II OMNIVORE study.