番茄社区

ORLANDO -- Responses to an immune checkpoint inhibitor continued for as long as 20 months after discontinuation for immune-related adverse events, according to a small retrospective study of patients with renal cell carcinoma (RCC).

Overall, eight of 19 patients had durable responses to PD-1/PD-L1 inhibitors after discontinuation. Eight others progressed 4 to 6 months after discontinuation, and the remaining three patients progressed soon after stopping treatment.

At the most recent follow-up, six of the eight patients with durable post-discontinuation responses remained free of disease progression, , of Dana-Farber Cancer Institute in Boston, reported at the (GUCS).

"These data show that responders to PD-1/PD-L1 targeted therapy can have persistent clinical benefit despite treatment discontinuation for immune-related adverse events," McKay said during a press briefing prior to GUCS. "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, or OMNIVORE."

The study highlights and important and critical issue in the use of immunotherapeutic agents to treat cancer, said press briefing moderator , an American Society of Clinical Oncology expert.

"There has been a tidal wave of new immunotherapies for cancer over the past several years, most commonly the PD-1 and PD-L1 inhibitors," said Pal, of City of Hope in Duarte, Calif. "These drugs work to reinvigorate the immune response, and they can have unintended consequences. Besides eliciting an immune response against cancer, they can elicit an immune response against organs in the body.

"Immune-related adverse events' impact can be serious but, as this study suggests, there is a possibility that a patient can have a protracted benefit in that the cancer remains dormant or shrinks," Pal added. "This supports the premise that whose who have immune-related adverse events could have a tangible benefit from the drug nonetheless."

PD-1/PD-L1 inhibitors have demonstrated efficacy in an expanding list of cancers. The standard approach to using the drugs is continuous treatment until disease progression or development of unacceptable toxicity, McKay noted.

As Pal pointed out, PD-1/PD-L1 inhibitors are associated with a variety of immune-related adverse events, thought to arise from immune-system activation. In some instances, the immune-related adverse events require treatment discontinuation. Little information has emerged about the clinical course of patients who discontinued an immune checkpoint inhibitor because of immune-related adverse events.

McKay reported findings from an analysis of patients treated with PD-1/PD-L1 inhibitors (primarily nivolumab) at five medical centers. Collective records from the five centers revealed 19 patients with metastatic RCC who initially responded to treatment but discontinued because of immune-related adverse events. Investigators categorized the patients according to how quickly the disease progressed after discontinuation: immediate progression if seen within 4 months; "other" when occurring from 4 to 6 months after discontinuation; durable response if no progression until after 6 months.

Patients' median age was 68, and all but one had clear-cell histology. Eleven patients had received systemic therapy prior to the PD-1/PD-L1 inhibitor, three had bone metastases, four had liver metastases, and five had aggressive/poor-risk disease. A majority of patients received single-agent treatment with a PD-1 inhibitor (N=11).

McKay's review of adverse events showed a dozen different types of events involving multiple organ systems. All but two patients required steroid therapy, two required additional immunosuppressive agents, and 10 of 19 had ongoing toxicity.

Response data showed an association between time on immunotherapy and duration of response after discontinuation. The eight patients who had durable postdiscontinuation responses had a median treatment duration of 11 months and median postdiscontinuation response of 20 months. Eight other patients had postdiscontinuation progression had a median treatment duration of 5 months and median time to progression of 4 months after discontinuation.

Three patients with immediate progression received treatment for 4 months and progressed a median of 2 months after discontinuation.

Comment