LITESPARK-005 Study Results and Thoughts on Second-Line RCC Treatment

A roundtable discussion, moderated by Brad McGregor, MD, focused on the latest data in RCC treatment and management, including data from the American Society of Clinical Oncology Genitourinary Cancers Symposium 2024. Dr. McGregor was joined by Rana McKay, MD; Elizabeth Wulff-Burchfield, MD; and Alan Tan, MD.

In the next segment of the roundtable series, the panel shared their thoughts on quality of life data presented from the LITESPARK-005 trial of belzutifan.

Watch the next segment in this series.

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Dr. McGregor: Pivoting a little more, we’ve talked a lot about the frontline setting. Despite adjuvant working and metastatic, there’s patients who still don’t respond to that frontline therapy. One of the more recent developments has been belzutifan. There’s interesting quality of life data. Libby, quality of life is critical.

Dr. Wulff-Burchfield: I think it was encouraging to see. The ultimate value of belzutifan has certainly not been realized as monotherapy and we’re going to learn more about that. In some ways right now, I sort of conceive of it as a TKI break, not just a treatment holiday, but an active therapy that also is a TKI break. I think that’s some of the way that I describe it to patients.

It was pretty consistent in looking at more global quality of life that it looks more favorable with belzutifan relative to ever everolimus. Some of the role functioning, physical functioning scores were a little bit more closely matched. Our colleague who presented that data had really valid points and concerns about the extent to which the metrics that we use and the tools that we use, while validated and in widespread use, and easy to compare, relatively easy to compare across trials, the extent to which that they capture all of the most important aspects of patient’s global well-being, I think is in question.

Just a little plug for the work of one of our other colleagues who has developed a pared down, more focused version of a combination of several important quality of life questionnaires. I think that there’s real potential to optimize that with time. But in general, I think it’s encouraging to see that an agent with a novel mechanism of action is going to be associated with a good and acceptable quality of life for our patients.

Participants in LITESPARK-005 had experienced multiple lines of therapy. These are folks who mimic the patients to whom we would offer this therapy.

Dr. McKay: I think what was really great too, is that, while historically the quality of life in these phase 3 trials have been exploratory endpoints, these were key secondary endpoints.

There was really some more rigor that was applied around the statistical analysis for these endpoints and the implementation of the quality of life instruments throughout the study. I do commend the study team for doing that. I think we do need to try to homogenize our RCC instruments across studies so we can better understand what they actually mean.

Dr. Tan: We’re all getting more experience now that it’s FDA approved. Some of us have been using it previously in VHL patients as well, but back to what Libby was saying, it’s so well tolerated that it’s almost like a TKI break, and these patients don’t have to usually discontinue the treatments  for other parameters.

Dr. McKay: Yeah. Just like fatigue, anemia, but a lot of the side effects that really haunt our patients. The diarrhea, the skin symptoms, the oral symptoms, the weight loss, are really not that evident with this agent. It’s very dose dependent. You stop the medication, things get better. It’s a good thing.