1. Perron, Michelle

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ORLANDO, Fla.-A small cohort study suggests that patients with advanced kidney cancer may experience more lasting benefit from immunotherapy than was previously believed. More research is needed, but these findings provide hope for patients who stop immunotherapy early to avoid side effects.

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The research was performed by Rana R. McKay, MD, and coauthors to assess the longstanding practice of continuing immune checkpoint inhibitor therapy despite severe side effects (J Clin Oncol 2017;35(Suppl 6S; Abstract 467)). McKay is Assistant Professor of Medicine at the University of California San Diego School of Medicine. She presented the findings in a presscast and a poster session at the 2017 Genitourinary Cancers Symposium, cosponsored by ASCO, the American Society for Radiation Oncology, and the Society of Urologic Oncology.


Study Design

Researchers followed a cohort of 19 patients with metastatic renal cell carcinoma that responded to immune checkpoint inhibitor therapy. The majority (63%) received PD-1/PD-L1 therapy as a standalone treatment, and 37 percent received PD-1/PD-L1 inhibitors in combination with other systemic treatments.


Patients spent approximately 5.5 months (median time for cohort) on immunotherapy. All patients stopped immunotherapy early due to immune-related adverse effects such as arthritis, uveitis, arthropathy, hypophysitis, myositis, blepharitis, hepatitis, rash, pericarditis, and amylase and lipase elevations.


"The patients in this cohort experienced a wide spectrum of adverse events affecting different organ systems," McKay explained at the presscast. The current standard of care is continuous dosing of immunotherapy treatment until disease progression or toxicity.


The researchers collected data on clinical characteristics, response, and survival data in all patients.


Patients were a median age of 68 years, and the majority (14) were men. Five patients (26%) had aggressive disease according to common diagnostic criteria, and more than half of the overall group (58%) had received prior systemic therapy.



After PD-1/PD-L1 treatment discontinuation, four (44%) patients remained progression-free with a median time off therapy of 20 months and a median time on therapy of 9 months (range of 4-15 months). Five (56%) patients experienced disease progression within 6 months of treatment discontinuation; median time on therapy was 4 months (range 3-10 months).


"We demonstrated that some patients can have persistent clinical benefit after discontinuation of PD-1/PD-L1 targeted therapy," the authors wrote. "Larger studies are warranted to evaluate the need for continuous drug dosing in all patients, to identify patients in which continuous dosing is not required, and to evaluate long-term outcomes in this population."


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


The moderator of the presscast, ASCO expert Sumanta Pal, MD, added the following: "This study is welcome news for patients who are unable to continue immunotherapy as a result of adverse effects. It's very reassuring to see that some patients may continue to benefit from immunotherapy even if they need to discontinue it. More broadly, these findings call into question the current standard of continuous treatment with immunotherapy, though longer-term follow-up is needed."


Immunotherapy Perspective

Scientists began exploring whether renal cell carcinoma might be a good target for immunotherapy when they observed that patients with metastatic renal cancer occasionally experienced spontaneous regressions after surgical removal of the primary tumor ( Cytokines have been used for more than a decade to treat kidney cancer. In the recent past, IL-2 was the most common first-line therapy for advanced kidney cancer, but due to the severity of side effects, it is generally reserved for cancers not responding to targeted therapies. Today, checkpoint inhibitors are at the forefront of advances in the treatment of renal cell carcinoma (Nature Reviews-Urology 2016; doi:10.1038/nrurol.2016.103).


Michelle Perron is a contributing writer.