Expert oncologists debate the significance of using quality of life as a metric when assessing patients’ responses to therapy for metastatic renal cell carcinoma.
Sumanta Kumar Pal, MD: When it comes to data, I’ve gone as far as calling this a fog factor. You’ve got PFS [progression-free survival], response rate, OS [overall survival]. But I want to talk about the quality-of-life [QoL] benefit for a moment. Brad, can you tell us what’s been going on in terms of the QL substudies in CheckMate 9ER?
Bradley A. McGregor, MD: All the patients who were in the study underwent PRO [patient-reported outcome] questionnaires. The scores were very similar at baseline. Patients were followed over time. There was a deterioration in quality of life in the sunitinib arm, but they maintain their quality of life in the cabozantinib arm, which is quite impressive. You’re doing this doublet therapy where I was really worried about the toxicities of TKI [tyrosine kinase inhibitor] plus I/O [immuno-oncology] therapies. And when you pair sunitinib—granted, it’s at the 4/2 [4 weeks on, 2 weeks off] dosing—we see improvement in quality of life with the combination arm vs sunitinib. It offers us the ability to have excellent disease control, with 6% progressive disease as best response, while maintaining quality of life for the patient, which is really important as we start looking at therapies to choose for our patients.
Sumanta Kumar Pal, MD: This quality-of-life issue comes up across every trial we look at. It’s an important characteristic. I was sitting with a group a few weeks ago, and they were nitpicking whether the quality-of-life metrics we’re using are actually relevant. I see Tom nodding, so I’m going to ask Tom what he thinks about quality of life.
Thomas E. Hutson, DO, PharmD: Quality of life is a great marketing tool. I was going to say something tongue in cheek to Brad: How many of the people who were progressing would say their quality of life was good if they were able to report that at time of progression? You have an agent like sunitinib where people are progressing much more frequently. They’re not going to be saying they have a great quality of life. The quality of life changes based on the efficacy of the agent in the person’s hand. We’ve all seen patients say, “Doctor, if it’s working, I’m on it. I don’t care what it’s like.” There’s a little factoring in that. We don’t know what to make of patient-reported outcomes yet. Everyone likes to talk about it. It’s a great marketing tool. But as far as making sure that they’re uniform and that we’re collecting them to make a great comparison of 1 drug vs another, I don’t know that we’re quite there.
Sumanta Kumar Pal, MD: By your logic, if you see that there’s no difference in quality of life with axitinib-pembrolizumab vs sunitinib, but there is with cabozantinib-nivolumab over sunitinib, is that purely driven by efficacy?
Thomas E. Hutson, DO, PharmD: Maybe. I don’t know. As far as I know, we don’t have PROs from the axitinib-pembrolizumab. That hasn’t been done. One question people brought up: Should we do a PISCES-type trial here? How would you even do such a thing? We all recognize the limitations of PISCES, but that was a brilliant marketing trial. That, along with the COMPARE study, really helped get people to believe in pazopanib as something that would be beneficial vs sunitinib. It’s along the same lines. It’s more of a marketing issue to me than something that’s going to make me choose 1 or the other. I’m going to use the drugs, and I’m going to gauge what the improvements are in my individual patients.
Sumanta Kumar Pal, MD: That’s interesting. It’s very controversial too. I’m going to jump on that and see if I can run with it a little. Tian, Tom says quality-of-life metrics are a marketing tool. Do you agree?
Tian Zhang, MD: If it is a marketing tool, it’s a very effective marketing tool. Either way, if the treatment is improving and controlling disease and that’s contributing to patients feeling better, that’s a win. If patients are tolerating the treatments pretty well in general, that’s a win. The common of the 2 cohorts is the TKI. I do think TKIs have significant adverse events associated with them. Patients learn to live with the adverse effects, but it is hard to tolerate these drugs. We often do a lot of dose reductions and monitor closely while patients start. Either way, if it’s from disease control or from tolerating the treatment well, it’s a good combination for patients.
Sumanta Kumar Pal, MD: Dave, I have to round out this question with you. Is quality of life just a marketing tool?
David F. McDermott, MD: It is a softer end point. It’s important to measure, but it would certainly be nice to look at quality of life longer if we could, particularly if patients can come off treatment. We don’t really follow that. It could be better. The harder end points are things like dose discontinuation and reduction. They’re easier to measure and suggest the patient isn’t doing well on treatment.
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