乌鸦传媒

As treatment options for metastatic renal cell carcinoma (RCC) have increased in number, selecting therapy has become more complicated.

At the American Society of Clinical Oncology (ASCO) annual meeting, researchers from a survey of more than 1,000 patients from 28 countries to demonstrate how patients' prioritization of treatment selection and how they define treatment success is crucial to improving patient-provider communication and to improving future drug development.

乌鸦传媒 brought together three expert leaders in the field for a virtual roundtable discussion: Moderator , from the Fox Chase Cancer Center in Philadelphia, is joined by , from the University of Texas MD Anderson Cancer Center in Houston, and , from the University of Texas Southwestern Medical Center in Dallas. This final of four exclusive episodes focuses on optimizing patients' quality of life in metastatic RCC.

Following is a transcript of their remarks:

Plimack: So we can't talk about treatments for renal cell carcinoma without talking about the holistic approach that we all take in clinic, which is to focus on the patient's quality of life. We want to keep them alive and feeling well and enjoying the things that are important to them for as long as possible. That's a shared goal we have with each of our patients.

And fortunately there is a lot of data on this -- a lot of it came out of ASCO. There were some really good education sessions around quality of life and optimizing that. And Dr. Zhang, we'll start with you. What were sort of the exciting pieces around this aspect of patient care that you saw at ASCO?

Zhang: Yeah, for me, quality of life and patient-reported outcomes really start with the patient. And so I thought there was a whole session devoted to patient perspectives and quality of life that I thought was really well done. And in particular there was a talk by Dena Battle who leads KCCure [Kidney Cancer Research Alliance], a really active advocacy group for kidney cancer that really has done a lot of great survey data to get patient perspectives in place. And so she talked a lot about what do patients want? And of course patients want a cure, but patients also want to set expectations about what to expect from their treatments. And so a lot of times we're collecting adverse-event data and percentages of how many patients have X or Y toxicity.

But it's really the global approach of, can we get patients living longer, but maintaining quality of life and getting them feeling well? So I thought her talk was really well-done, and one of her driving points was stop thinking about treatment toxicity as a trade-off. Like how much am I willing to accept for X amount of progression-free time or X amount of number of years lived longer. And her point was really that if a curative therapy comes with a certain degree of toxicity, then that patient actually [is] more receptive of toxicities. And it's just a discussion about what to expect for those patients with each of these treatment lines.

Plimack: Yeah, I thought that was a really great point from her talk. Dr. Shah, what are your thoughts around quality of life and some of the data from ASCO?

Shah: Yeah, absolutely. If you talk about one impactful slide, it was Dena Battle's slide where it kind of had "patients are willing to undergo a toxicity if we're talking about curative, intense strategies." And it was just a very impactful slide and I thought really beautifully discussed.

This is tough. I think this is really tough, because I think on one hand, you're right, we've made a lot of progress in the field of kidney cancer. We have a lot more therapies up our sleeve. We're getting better at managing toxicity when IO [immunotherapy] came out and we didn't know what we were doing initially, but that feels easy now to kind of manage a lot of these issues. That being said, for most patients, cure is not something we're discussing in the metastatic setting, and the daily cumulative toxicity that our patients face is significant.

So I think it does still remain front and center even as we evolve in the field. Dr. [Elizabeth] Wulff-Burchfield had a really beautiful discussion -- and I know I struggle with all these different PROs [patient-reported outcomes] and quality-of-life metrics. Sometimes it's hard to really parse out what it's showing, and the data is dissected. And she had a really beautiful talk on just "here's how you follow the trend" and "here's what we should be getting out of these surveys." And so that was great too.

I will say, just from a very practical perspective, we've had a couple of posters and data sets now that have shown that TKI [tyrosine kinase inhibitors] dose reductions do not significantly impact your outcome. And I think that's really important for our patients, that if you need a little weekend-break strategy or dose-reduction strategy for patients on chronic TKI, it does wonderful for their overall quality of life without hopefully sacrificing too much on the efficacy front.

Plimack: Absolutely. I mean, I'll just echo both your comments. I think the point that Dena Battle is getting at -- I tell my fellows we treat for efficacy, we pick the most effective for that patient based on all the discussions we just had around the frontline, second-line choices. And then you manage for toxicity, because you can never quite predict which of the many side effects -- with all our agents that we list for patients -- they're going to get or how impactful they'll be for their specific situation. And the dose reduction is a tool we use all the time with TKI therapy -- of course not with IO -- but with TKI.

And then the one thing I really hope is that we evolve a way of defining toxicity that is not just severity-dependent, but time-dependent. So right now with CTCAE [Common Terminology Criteria for Adverse Events], if you have grade IV diarrhea for a day, it's a grade IV diarrhea event. If you have grade II for 2 years, it's a grade II event. And that really just doesn't describe the impact on the patient with respect to the agent.

So I don't think we're getting the full picture around toxicity, because we're missing that duration point. And then what we can't measure is how impactful a specific side effect is to a given patient. One patient may not care at all about a hoarse voice, but someone who sings may find that intolerable. So these are the things that we manage with our patients.

And the other thing I'm hoping we see improve with the patient-reported outcomes is -- one thing that's always struck me -- is our patients fill [the forms] out diligently while they're coming in and while they're on the study. And then when they go off the study -- maybe for an excellent response, maybe their quality of life gets better -- but they're not telling us, because they're not filling out the forms. Or maybe they're admitted to the hospital with terrible enterocolitis. They're not filling out the forms in the hospital, so that also isn't documented. So we're really only documenting patient-reported outcomes for patients stable on treatment, filling out those forms.

Again, I hope we can evolve how we document these things to better codify it in the data. But I agree with both of you, it's a patient-to-patient conversation that you manage in real time, ongoing. As Dr. Zhang said, if someone's responding really well and doing great, they're willing to manage with more toxicity, perhaps, than someone who isn't, or adjuvant setting versus metastatic setting. So yeah, the art of oncology for renal cell.

Zhang: Absolutely. Dr. Plimack, if I could, I would just add also that there's a role for real-world data collection in a careful way. So there's a study out there that we're participating in and that I helped design when I was at Duke called . And it's collecting patients throughout the PCORnet -- the Patient-Centered Outcomes Research Network that was established by Medicare -- to really look at how patients travel through their journey with kidney cancer.

And to your point that we're not getting these patient-reported surveys filled out when they're in the hospital or off a treatment, this ODYSSEY study will collect 800 patients, follow them prospectively all while they're starting their first-line treatment for metastatic disease but then also along the course of their journey with kidney cancer. So if they're coming off a treatment or if they're going on a different treatment, it'll capture that and it'll capture some of their -- intervally -- their quality of life during all of their treatments and even off of treatment.

So to your point, it's so important to follow these patients in a longitudinal fashion. We don't know what happens to them when they're off-trial and I'm hoping some real-world data will help us.

Plimack: Absolutely. That's a brilliant trial design in the way it follows patients across the spectrum of their treatment. I think that's unprecedented and a really great idea and great effort.

Shah: And Dr. [Michael B.] Atkins has, I think, been a bit of a pioneer in his study design of building in treatment breaks and really tracking that treatment-free survival. And I think that's equally important too, because a lot of our trials right now are sort of chronic. And so where can we take those breaks? Where can we really allow the quality of life to improve while still keeping the disease controlled is I think...

Plimack: And when is it safe to stop? We don't have time to talk about that, but that's a whole other topic that we're trying to have data to support the decisions they make. But right now we're kind of making them on our own. But yes, treatment-free survival is what we want for everyone really.

Great. Thank you. Great discussion. Thank you.

Click here to watch the other videos from this ASCO roundtable series on RCC.

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