Considerations for Managing Patients on Maintenance RCC Therapy

A roundtable discussion, moderated by Katy Beckermann, MD, PhD, discussed the treatment sequencing, management, and future directions of advanced or metastatic kidney cancer, as well as relevant clinical trial data from the 2024 American Society of Clinical Oncology Annual Meeting. Dr. Beckermann was joined by Yousef Zakharia, MD; Pavlos Msaouel, MD, PhD; Benjamin Maughan, MD, PharmD; and David McDermott, MD.

In the third segment of the roundtable series, the panel offers evolving strategies for managing treatment durations and holds for patients on IO/TKI and PD-1 inhibitor regimens, highlighting the influence of clinical trial data, patient-specific factors, and the need for more conclusive research.

View the next segment on Personalized RCC Care: Decreasing Overtreatment, Identifying Cured Patients in the Adjuvant Setting.

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Dr. Beckermann: We talked earlier about timing and how long people should remain on IO/TKI regimens. Most people stay on TKI as per trial protocols. How do you manage patients on maintenance PD-1? Do you continue as the trial did or stop at 2 years?

Dr. Zakharia: My practice has changed over the last 5 years. Initially, based on the CheckMate 214 data, we continued PD-1 inhibitors like nivolumab as long as the patient tolerated it and the tumor responded. Now, with more experience and data, such as Dr. McDermott’s treatment-free survival data, we feel more comfortable holding treatment. Sometimes, I do not continue up to 2 years if there is a deep response on 2 subsequent scans. After discussing with the patient, I often give them a break, and I have not regretted this approach. In a few cases where the disease progressed, rechallenging with nivolumab was beneficial.

I have not applied this approach to IO/TKI yet. I am more hesitant to hold the TKI part, especially in cases with high disease bulk. While I am comfortable holding immunotherapy based on trials like CLEAR, which stop pembrolizumab at 2 years, I am still hesitant to stop the TKI early on.

Dr. Maughan: That raises a question. Do you handle treatment holds differently for ipi/nivo versus IO/TKI? In my practice, I seek treatment holidays at 2 years for ipi/nivo. For IO/TKI, lacking immunological synergy, I feel compelled to continue both treatments as long as they are effective. If I stop anything, it is typically the TKI due to side effects.

Dr. Zakharia: We often hold or reduce TKI doses due to side effects, and there is enough real-world data showing this does not impact efficacy. However, I am hesitant to completely stop TKI, though I am more comfortable holding IO for longer periods.

Dr. Maughan: Do any of you do it differently?

Dr. Msaouel: I agree with the points raised. For instance, in the CLEAR trial with pembrolizumab and lenvatinib, we stop pembrolizumab at 2 years because insurance typically will not cover beyond that. The 2-year cutoff is arbitrary, but it serves as a useful landmark. With nivolumab maintenance post-ipi/nivo in responding patients, it is patient-dependent and involves clinical factors. If there is disease activity around the 2-year mark, stopping therapy might not be wise as it is hard to discern whether changes are due to stopping treatment.

Dr. Beckermann: Dr. McDermott, do you think stopping pembrolizumab or nivolumab and cabozantinib-nivolumab at 2 years affects the tail of the curve?

Dr. McDermott: It could, but we need more study data on this. Early PD-1 data in melanoma showed 90% of patients stayed in response after stopping at 2 years, but in kidney cancer, that number is lower, around 50%. We need real data, which might not require a prospective industry trial but could be collected from existing practice. Lack of data complicates treatment decisions, and insurance often denies rechallenging, which is why prospective data is crucial.

Dr. Beckermann: Each frontline trial has shown that significant tumor shrinkage correlates with outcomes similar to complete responses. For deep responses in IO/TKI patients, I feel more confident discussing treatment breaks, considering patient concerns and current side effects.

Dr. Maughan: Comparing immune therapy in melanoma versus kidney cancer, responses differ significantly. CheckMate 025’s long-term data showed low progression-free survival at 7 years, unlike melanoma, indicating the diseases are different.

Dr. McDermott: We need more data to conclusively prove CTLA-4’s benefits. Trials like CheckMate 8Y8 will inform us, but we must keep pushing for information to benefit our patients.