Some Stop Immunotherapy, Still Have Controlled Cancer

Nick Mulcahy

February 14, 2017

Some patients who respond to cancer immunotherapy with checkpoint inhibitors can have "persistent" clinical benefit even after they stop therapy because of immune-related adverse events, according to new research.

Among 19 patients with advanced kidney cancer who had a treatment response with PD-1 or PD-L1 immunotherapy but then stopped the treatment early because of adverse events, nearly half (42%, n = 8) had a durable response, which means these patients remained off any additional systemic therapy for 6 months or longer. There was one complete response and seven partial responses.

Furthermore, 6 of those 8 durable responses have been ongoing, with the patients free from progression.

Among the eight patients with durable responses, the median time on treatment was 11 months, and the median time subsequently off treatment was 20 months.

"The greatest take-away message from the study...is that there is a subset of [patients] who continue to have disease that is in check and controlled despite their not being on any therapy...," said lead study author Rana R. McKay, MD, assistant professor of medicine at the University of California, San Diego, School of Medicine.

Prospective trials are needed to investigate the discontinuation of therapy as a treatment approach, she added while discussing the new study at a presscast that preceded the Genitourinary Cancers Symposium (GUCS) 2017, which will be held later this week in Orlando, Florida.

"Further research is needed to validate this phenomenon," echoed Sumanta Pal, MD, a medical oncologist at the City of Hope Cancer Center in Los Angeles, California, who moderated the presscast

"But certainly this [result] supports the premise that those individuals who do experience immune-related side effects could have a tangible benefit nonetheless," he added. Dr Pal is also an expert for the American Society of Clinical Oncology, which organized the symposium.

Studies have been planned that will attempt to validate the findings. The phase 2 OMNIVORE study (Optimized Management of Nivolumab Based on Response in Patients With Advanced Renal Cell Carcinoma) will investigate customization strategies, said Dr McKay.

In effect, it appears that there may be potential challenges as to how immunotherapy is given.

"The current standard is to administer treatment on a continuous basis until progression or toxicity," said Dr McKay.

Toxicities include immune-related adverse events, which are caused by activation of the immune system. All 19 study patients stopped immunotherapy early because of such adverse effects, which included joint pain; eye problems; inflammation of the pituitary gland, muscle, heart, liver, pancreas, kidney, or lung; and diarrhea.

Sixteen patients (84%) required steroid treatment, and two (11%) required additional immunosuppressive agents. More than half (53%) have ongoing health problems related to toxicity.

The patients were mostly men (74%), and the median age was 68 years. Nearly all patients had cancers of clear-cell histology.

The majority (63%) received PD-1/PD-L1 therapy as a monotherapy; 37% received PD-1/PD-L1 inhibitors in combination with other systemic treatments. Overall, the median time on immunotherapy was 5.5 months.

The study was funded by kidney cancer SPORE (Specialized Program of Research Excellence) grants from the Dana-Farber/Harvard Cancer Center; the Trust Family; Michael Brigham; and Loker Pin. Several study authors have financial ties to industry, including Bristol-Myers Squibb and Roche/Genentech. Dr Pal has financial ties to multiple pharmaceutical companies.

Genitourinary Cancers Symposium (GUCS) 2017. Abstract 467, to be presented February 18, 2017.

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