Transcript: Daniel J. George, MD: I want to switch gears now a little bit to pivot toward patient-reported outcomes, because some of that is being reported at this meeting as well. In general, Joe, what’s your take on the PRO [patient-reported outcomes] data from these trials? Do you feel that it’s moving the bar 1 way or the other in your treatment decision? Are there signals you didn’t pick up with the AE [adverse events] assessments?

Chung-Han Lee, MD, PhD: Yes, I really feel that for the patient-reported outcomes, a lot of that is picked up within the patient assessments. I think that largely, in treating the patients on the trials, we’ve gotten the sense of how they do, how toxic the drugs are, and whether the patients feel better overall. You get the sense already. Certainly it’s great to be able to objectively quantify this, and that patient can report to you in a more systematic sort of way, but it’s kind of giving numbers to what we probably had a sense for already.

Daniel J. George, MD: When we looked at CheckMate 214, the patient-reported outcomes actually improved over time, and some of that may be intuitive because you’re dropping ipilimumab, but some of that is also the fact that we’re not getting the cumulative toxicity so much, and maybe we’re acclimating a little bit to this and seeing these patients actually improve their quality of life on that.

Chung-Han Lee, MD, PhD: Yes, the improvement in quality of life is 2-fold. One is, if you’ve been on these treatments—especially IO [immuno-oncology] therapy for a prolonged period of time—likely you’ve had tumor shrinkage over this time and you probably have [fewer] symptoms related to the disease. The other part of it is in comparison—like long-term TKI [tyrosine kinase inhibitor] therapy is not easy. A lot of people, when they come off and have to make that switch to something else and get that break, remember what it’s like to not be on a TKI.

Nizar M. Tannir, MD, FACP: I’ll add, too, about the quality of life and the outcome with that research. At the end what matters the most is efficacy. I mean, No. 1 is efficacy. Dan, you brought up atezolizumab plus bevacizumab—the IMmotion151 phase III trial. I believe that is the most tolerable regimen. You will all agree that atezolizumab-bevacizumab is very tolerable with the lowest adverse-events profile. However, until it’s approved, you can present all beautiful quality-of-life data, but it’s not approved because it did not lead to OS [overall survival] benefit. Maybe with longer follow-up we will see that, but until then, it’s not really helpful for me in my algorithm or my selection process for phasing. At the end—first, patients want to be cured; second, they want to live longer and be able to be off therapy and maintain that treatment-free survival we’re talking about. Then I think we can talk about quality of life.

If you have 2 equivalent therapies, yes, I’ll pick the 1 that produces the best quality of life with the least cost, but if 1 therapy is not approved—didn’t have the efficacy—it’s not relevant to me to really put much credence into the quality of life.

Robert S. Alter, MD: However, I’ll definitely say then, we all believe that you’re taking care of the patient who has the cancer, not the cancer itself. I think that despite the patient-reported outcomes that we hear, we’re becoming more familiar with the toxicity of the therapy. We’re more cognizant to our patient care. And I tell my patients, “If you cannot tolerate the medicine, no matter how well it works, the medicine cannot be given.” I think, until we get the efficacy data, until we get them to their first scan or second scan, we have to make sure they tolerate it. Even though we don’t have PROs in all the patients, I think in all the clinics we are definitely making sure that their quality of life is the most important initially, to make sure they can enjoy more therapy to actually maintain their responses.

Daniel J. George, MD: Nice. That’s a great point.

Chung-Han Lee, MD, PhD: One of the things I tell my patients all the time, when we talk about whether or not to do that dose reduction—especially if they’re on the fence, because no patient ever is happy about the idea of going down on the dose—is, “Could you imagine living a year like this?” And the answer is, “No.” Then it really does mean that I probably do need to lower that dose for you.

Robert S. Alter, MD: I see. I tell them they’re walking a marathon. It’s not how fast you start the race; it’s that you can finish the race. To get there, slowly but healthy is probably the better way than just trying to get the quickest response and becoming more toxic.

Daniel J. George, MD: And you know, it brings up another point. We’re talking about frontline therapy, but it’s not necessarily their last regimen, right? For these patients—responding, tolerating therapy—long term is key because at some point, if they do progress, there’s going to be an opportunity to treat them with sequential therapy.Transcript Edited for Clarity