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Benefits of immunotherapy for advanced kidney cancer may persist after therapy cessation
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Patients with advanced kidney cancer who stop PD-1/PD-L1 immune checkpoint inhibitor therapy prematurely due to adverse events may be able to remain off additional systemic therapy for 6 months or more without disease progression, according to a small cohort study scheduled for presentation at the Genitourinary Cancers Symposium.
“The greatest takeaway from our study is that there are patients who can experience toxicity to PD-1/PD-L1–targeted therapy that results in overactivation of the immune system and actually needing to stop treatments,” Rana McKay, MD, assistant professor of medicine at University of California, San Diego School of Medicine, said during a press conference. “What we’ve demonstrated is that, despite these patients stopping their treatments, there is a subset who continue to have disease that is in check and controlled, despite not being on any therapy. Those are the durable responders: 42% of patients, when they stopped their treatments because they had some toxic event, were actually able to remain off any other cancer-targeting therapy for over 6 months with their disease being controlled.”
Current standard practice for immune checkpoint therapy is for patients with metastatic renal cell carcinoma to continue treatments of nivolumab (Opdivo, Bristol-Myers Squibb) — a monoclonal antibody against PD-1 — on a continuous basis until progression or toxicity.
Outcomes of patients who experience a response to treatment and then discontinue therapy for immune-related adverse events had not been fully characterized. McKay and colleagues sought to evaluate outcomes of responders to PD-1/PD-L1–targeted therapy who discontinued treatment.
Researchers analyzed data from 19 patients with advanced metastatic renal cell carcinoma who responded to immune checkpoint inhibitor with tumor shrinkage of least 30%. Twelve patients (63%) received PD-1/PD-L1 monotherapy, and seven patients (37%) received PD-1/PD-L1 inhibitors in combination with other systemic treatments.
The median time on immunotherapy was 5.5 months. All patients stopped immunotherapy early due to immune-related adverse events, such as joint pain; eye problems; inflammation of the pituitary gland, muscle, heart, liver, pancreas, kidney or lung; and diarrhea.
Four patients (21%) experienced disease progression immediately after treatment stopped.
Eight patients (42%) showed a durable response and remained off additional therapy for at least 6 months, four of whom remained progression free with a median time off therapy of 20 months (range, 10-44) and median time on therapy of 9 months (range, 4-15). Five patients progressed within 6 months (range, 2-6) of therapy discontinuation after a median time on treatment of 4 months (range, 3-10).
“Overall, with regard to the durable responders, 75% of patients were free from progression,” McKay said.
McKay and colleagues demonstrated that some patients can have persistent clinical benefit after discontinuation of PD-1/PD-L1–targeted therapy for immune-related adverse events, but noted the need for larger studies to evaluate the need for continuous drug dosing in all patients and long-term outcomes of those who discontinue treatments.
“Our subset was small — only 19 patients — so next steps would be to validate our findings in a larger study and conduct a prospective trial assessing whether discontinuation of therapy is something that is worthwhile to investigate in this population,” McKay said.
PD-1 and PD-L1 inhibitors play a prominent role in the “tidal wave” of immunotherapies that have developed in recent years, Sumanta Pal, MD, associate professor of medical oncology at City of Hope Comprehensive Cancer Center, ASCO expert, and a HemOnc Today Editorial Board member, said during the press conference.
“One of the unintended consequences is that besides eliciting an immune response against cancer, they may also potentially elicit an auto-immune response against one or multiple organs in the body,” Pal said. “But there is the possibility [patients] can have a protracted benefit of the drug in terms of their cancer remaining dormant or shrinking for a protracted period of time. Further research is needed to validated this phenomenon, but this supports the premise that those individuals who do experience immune-related side effects could have a tangible benefit from the drug nonetheless.” – by Chuck Gormley
Disclosure: McKay reports research funding from Bayer and Pfizer. Please see the abstract for a full list of all other researchers’ relevant financial disclosures.