Advanced Clear Cell RCC: Quality of Life Data in First-Line Clinical Trials

Transcript:
Thomas Powles, MD: Let’s talk about quality of life.

Rana McKay, MD: Yes.

Thomas Powles, MD: What’s going on with quality of life? Are we measuring it right? What does it show?

Rana McKay, MD: I don’t think we know yet how to measure it. When we look at all these trials, quality of life assessments have been exploratory analyses in the context of these trials. They have not been defined as primary end points in any way, shape, or form, or even secondary end points for that matter, with robust statistics set up a priori around how to interpret the quality of life data. When we look at the quality of life data across the IO/IO [immunotherapy combination] and IO/VEGF trials, one, the instruments are all different. We haven’t standardized metrics for which instruments to use, from EORTC [European Organisation for Research and Treatment of Cancer] to the disease symptom score, functional scores, pain scores. Also, the timing of when the instruments were deployed within the clinic, within the context of the trial, was it at baseline? Is it every 3 weeks? Is it every 6 weeks? In the sunitinib control arm people are on a 4/2 [week] schedule. Sometimes for some studies, they’re filling out the instruments after the 2-week hold, sometimes they’re not. I think [we should] caution against the inter-trial comparisons, because there has not been consistency across all the trials with the instruments, the timing, and even looking at the outcome measured, like time to first deterioration, time to confirmed deterioration, time to definitive deterioration, these mixed modeling methods. There’s a lot of confusion around it….

Thomas Powles, MD: I agree.

Rana McKay, MD: But in summary, I think these were randomized studies. They were randomized to a control arm, and within the context of each of these individual studies, we have seen that quality of life seems to be improved with the [CheckMate] 9ER data, nivolumab and cabozantinib, compared to sunitinib. I think those patients were probably more symptomatic. There were more poor-risk patients, so they had less favorable patients. You treat the disease, the patient is going to feel better. Similarly, with [CheckMate] 214, patients actually do well when they get through their ipi [ipilimumab] and they’re on maintenance nivolumab. They do quite well from a quality of life standpoint. The data for len-pem [lenvatinib and pembrolizumab], in some of the domains there seemed to be some improvement; most of it appeared to be equivalent to sunitinib, the KEYNOTE-426 data were basically that it was largely similar to sunitinib.

Thomas Powles, MD: That sounds good to me. In summary, we need better tools, but overall, the quality of life seems to be maintained providing the cancers aren’t progressing. There are some subtle differences maybe between ipilimumab and nivolumab and the VEGF TKIs [tyrosine kinase inhibitors].

Eric Jonasch, MD: I would make a plug there that the patient voice in how these instruments are developed is critical. There are academic exercises, and having the patients who are going to be undergoing these involved in the development of them, so that the outputs we get are interpretable and meaningful. We as physicians I think struggle with a 2-point difference in some of these. What does that mean for a patient? This has to be contextualized, and I think we can really improve.

Transcript edited for clarity.