Discontinuing Immunotherapy Because of Adverse Effects May Not Compromise Efficacy

Orlando, FL—The current practice in the treatment of advanced kidney cancer and some other cancers is to continue treatment with immune checkpoint inhibitors until disease progression, and sometimes even longer. However, the results of a new, preliminary trial call this practice into question by suggesting that the benefits of immunotherapy can continue in some patients, even if treatment is stopped prematurely.

The study, presented at the 2017 Genitourinary Cancers Symposium, included an international cohort of 19 patients with metastatic renal-cell carcinoma who responded to initial treatment with nivolumab-based immunotherapy, but stopped treatment because of immune-related adverse effects.

Among these patients, 42% had a durable response, defined as time not receiving therapy for ≥6 months, according to Rana R. McKay, MD, Medical Oncologist and Assistant Professor of Medicine, University of California San Diego School of Medicine, La Jolla.

Although the persistence of response after discontinuing immune checkpoint inhibitor therapy has been reported anecdotally, this is the first systematic study to evaluate the outcomes of patients with metastatic renal-cell carcinoma who stop anti–PD-1/PD-L1 immune checkpoint inhibitor therapy because of immune-related side effects, Dr McKay and colleagues noted.

“In medicine, we are constantly balancing the benefits and risks of any given treatment. This is a small study, and our findings need to be validated in a larger group of patients, but it underscores that, in some cases, immunotherapy can have lasting benefits even after treatment discontinuation,” Dr McKay stated.

Patients had received nivolumab either as monotherapy (63%) or in combination with other systemic treatments (37%). The median time receiving immunotherapy was 5.5 months. All 19 patients discontinued treatment because of immune-related adverse effects, which included joint pain, rash, eye problems, diarrhea, and inflammation of the pituitary gland, muscle, heart, liver, pancreas, kidney, or lung.

Steroids were administered to 84% of patients, and additional immunosuppressive agents were required for 11%. More than half of the group had ongoing toxicity at the time of the analysis.

In 3 (16%) patients, the tumor pro­gressed immediately after stopping treatment, but 8 (42%) patients had a continued (durable) response ≥6 months posttreatment. Patients with a durable response spent a median of 11 months receiving treatment and 20 months not receiving treatment, Dr McKay reported. The remaining 8 (42%) patients did not receive treatment for 4 to 6 months, or had follow-up for <6 months.

“We demonstrated that responders to anti–PD-1/PD-L1 agents can have persistent clinical benefit despite treatment discontinuation for immune-related adverse events,” Dr McKay said.

She and her co-investigators hope to include more patients in this analysis so that they can identify the clinical characteristics associated with a durable response to immunotherapy.

A prospective phase 2 trial called OMNIVORE (Optimized Management of Nivolumab Based on Response) is planned to further explore the efficacy of immunotherapy after treatment discontinuation in patients who respond to treatment.

“This study is welcome news for patients who are unable to continue immunotherapy as a result of adverse effects. It is reassuring to see that some patients may continue to benefit from immunotherapy, even if they need to discontinue it,” said press cast moderator Sumanta Pal, MD, Co-Director, City of Hope Kidney Cancer Program, Duarte, CA.

Dr Pal emphasized that although the “unintended consequences of a reinvigorated immune response [ie, immune-related adverse events] can be serious,” patients with these side effects “can still have tangible benefit from these drugs.”

“More broadly, these findings call into question the current standard of continuous treatment with immunotherapy, although longer-term follow-up of patients is needed,” Dr Pal said.