Long-Term RCC Control With Immunotherapy, Despite Early Discontinuation

Immunotherapy offers durable responses lasting more than 6 months after treatment discontinuation for some patients with metastatic renal cell carcinoma (mRCC), according to findings from a small cohort study that will be presented at the 2017 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held February 16–18 in Orlando, Florida (abstract 467).

In this study of 19 patients with mRCC who discontinued programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1)–targeted immune checkpoint blockade due to immune-related adverse events (irAEs), 8 patients (42%) experienced sustained tumor control without additional systemic therapy for at least 6 months, the authors reported.

“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 after treatment discontinuation,” said Rana R. McKay, MD, of the University of California, San Diego School of Medicine.

The current standard of care is continuous dosing of treatment until disease progression or toxicity. Larger studies are needed to “evaluate the need for continuous drug dosing in all patients,” to identify which patients can benefit from noncontinuous dosing, and to evaluate long-term outcomes for different treatment regimens, noted McKay. The authors are planning a prospective clinical study to confirm and further explore the findings.

Of the nine patients studied, eight patients had clear cell histology and one patient had translocation RCC. Seven patients had not undergone previous treatment.

Median treatment duration was 5.5 months. Four patients received PD-1/PD-L1 inhibition monotherapy, while the others received combination therapy with other agents. One patient experienced a complete response, while seven others had partial responses and one patient had stable disease with a 17% decline in tumor diameter.

Treatment discontinuations followed the emergence of irAEs such as arthritis; uveitis; diarrhea; inflammation of heart, liver, pancreas, muscle, kidney, and lung tissue; rash; and pituitary toxicity.

“After PD-1/PD-L1 treatment discontinuation, four (44%) patients remained progression-free with a median time off therapy of 20 months (range, 10–44 months), and a median time on therapy of 9 months (range, 4–15 months),” McKay reported. Five (56%) patients progressed within 2 to 6 months of treatment discontinuation, with a median treatment duration of 4 months (range, 3–10 months).

The study is “welcome news” for patients who must halt immunotherapy because of irAEs, commented ASCO expert Sumanta K. Pal, MD, of City of Hope in Duarte, California. “It’s very reassuring to see that some patients may continue to benefit from immunotherapy even if they need to discontinue it.”

While larger studies and longer follow-up times are needed, the findings raise questions about the current standard of continuous immunotherapy until tumor progression, said Pal.