Nivolumab and salvage nivolumab plus ipilimumab for aRCC

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Published: 18 Feb 2023
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Prof Michael Atkins - Georgetown Lombardi Comprehensive Cancer Center, Georgetown, USA

Prof Michael Atkins speaks to ecancer about the treatment-free survival (TFS) outcomes from the phase II study of nivolumab and salvage nivolumab plus ipilimumab in advanced clear cell renal cell carcinoma at ASCO GU 2023.

Significant TFS was reported for the CheckMate 067 trial in patients with metastatic melanoma and the CheckMate 214 trial for patients with aRCC, but treatment was often stopped for toxicity rather than a pre-defined treatment endpoint.

In this study, they assessed TFS in the HCRN GU16 260 trial, which was designed to reduce toxicity and to cap immunotherapy duration.

Nivolumab monotherapy with salvage nivolumab plus ipilimumab in non-responders is an active treatment approach in treatment-naïve patients with aRCC and results in substantial TFS and toxicity-free TFS.

TFS was particularly noted in patients with favourable risk disease, further supporting the use of an immunotherapy-only regimen in this population.

I’m talking about the HCRN GU16 260 trial which was a phase II trial of nivolumab monotherapy followed by a nivolumab/ipilimumab boost in patients with clear cell metastatic kidney cancer. The clinical results of this trial were published in The Journal of Clinical Oncology in April of 2022. What I’m talking about at this meeting is the results of a correlative analysis looking at treatment-free survival in this study.

What we’ve known for a while is that immunotherapy is unique in that patients can have durable control of their disease after treatment stops. They also sometimes can experience toxicities that persist after treatment stops. Treatment-free survival was developed as an endpoint that could look at what goes on during that treatment-free period. We’ve looked at this in other studies in patients with melanoma and kidney cancer using immunotherapy, but those studies were compromised because the treatment was only stopped for toxicity or disease progression and there was no defined treatment endpoint. So we wanted to look at that in this study because treatment stopped at a maximum of about 96 weeks, and see how that influenced treatment-free survival.

We have updated this study through 37.7 months and looked at a 36 month period for the 128 patients enrolled. We defined treatment-free survival as the area between two time to event endpoints: the time from treatment study registration until treatment cessation, and the time from study registration to starting subsequent therapy over a 36 month period. When we looked at the updated clinical data, and we wanted to combine part A and part B in this study into one regimen, and we saw the overall response rate was 36%, 58% in the favourable risk population, 27% in the intermediate and poor risk population. 68% of all patients were alive, and 38% of patients were alive without having begun subsequent therapy, and all patients had finished treatment. When we looked at that 36-month time frame we saw that for the average patient 30 months of that 36 month time period was spent alive and those 30 months were divided into timeline treatment 11.5 months, treatment-free period 9.5 months, and time on subsequent therapy 9 months, adding up to 30 months. When we looked at it for the favourable risk patients, we saw that the treatment-free survival period was 12.9 months, or 36% of that total 36 month period, and that 99% of that time was spent alive; there was only one death in those favourable risk patients which occurred at 28 months. While in the intermediate and poor risk patients, treatment-free survival represented around 22% of that 36 month period.

When we compared those results to the results of CheckMate 214 on the ipilimumab/nivolumab arm, the treatment-free survival compared favourably, illustrating the value of having a treatment cessation endpoint. 

We feel that treatment-free survival is a valuable endpoint that contributes meaningful data to a clinical trial beyond what is captured with traditional endpoints. Therefore, we think it’s something that should be considered in all immunotherapy trials, and potentially all trials, not just in kidney cancer but potentially other diseases. The second point that I think came from this study was how well the favourable risk patients did both in terms of overall survival and treatment-free survival, supporting the notion that there should be an immunotherapy-only treatment approved for that patient population.