Treatment Strategies for Patients With RCC and Brain or Bone Metastases


Drs Barata and Ornstein describe how they treat certain subgroups of patients with advanced RCC, particularly those with brain or bone metastases.

Tian Zhang, MD: Dr Barata, maybe you can take a minute more to tell us briefly about patients with poor performance status or some patients with hematuria and your approach to those subgroups.

Pedro C. Barata, MD, MSc: That’s a great question because we can spend all day talking about trial data, but then what we do with patients that come to us, and we all see them every day who don’t meet the criteria for clinical trials, I guess performance status is one of them. All these studies for the most part excluded patients with frail are defined by performance status of 2 or higher and what we do in those cases. I guess one of the data we can use to shed some light into this topic is the data that was presented by our friends from Europe, a European study that basically took about 50-plus patients, treated with either ipi/nivo [ipilimumab (Yervoy)/nivolumab (Opdivo)] and axi/pembro [axitinib (Inlyta)-pembrolizumab (Keytruda)] in the context of a PS, performance status, too, and above and actually that study is very interesting because it shows a couple of things. First, what we see every day and these patients tend to be less often offered nephrectomies and in general are mainly intermediate and poor risk, so a lot of this has to do with symptomatology with the disease. Patients who are very symptomatic and not doing well and actually crashing in front of us, and interestingly enough when we look at the efficacy outcomes in particular in that study, we can see that all the end points, including response rate, are much lower whether you use ipi/nivo [ipilimumab/nivolumab] or axi/pembro [axitinib/pembrolizumab] in this case. Thus, the other interesting point is perhaps unexpected to some extent, we didn’t see much of a difference in terms of efficacy whether we think of ipi/nivo [ipilimumab/nivolumab], whether we use axi/pembro [axitinib/pembrolizumab] in those patients.

If I were to answer in general to your question, in some situations where we believe that by offering full dose upfront which sounds like there is a common answer from us for most individuals, in some circumstances I’ve started at the lower dose and then after I trade if needed. That’s basically applicable to the TKI [tyrosine kinase inhibitor] partner in general unless we’re thinking of ipi [ipilimumab], but any PD-1 [programmed cell death protein 1] inhibitor in general we offer the flat dose even for patients with poor performance status. But I dose titrate the TKI in scenarios where I could harm the patient. And then, if the patient is [not doing well], I can quickly up titrate if needed but I just wanted to highlight that data, which was just presented at ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium], and is a European study that kind of gives us some helpful information about how different combination regimens behave in that patient population, very hard to treat.

Tian Zhang, MD: Sure. And this is a real-world pragmatic approach to how we get drug into our patients unless they’re actually taking them or continuing on treatment. We can see all the efficacy in trials but unable to see them in our patients until they get them in hand and in their mouths. Great, and Dr Ornstein, why don’t you also fill us in about patients with brain and bone metastases because these are particular subgroups that we are thinking of across the board and many of our colleagues are in dealing with these particular situations.

Moshe C. Ornstein, MD, MA: Brain metastases are a real challenge for our patients, not just clinically and in terms of their outcomes, but also because the trials generally do not enroll patients who have brain metastases. They might allow for them after the brain metastases are treated, but it’s hard to gauge what the response of any of these TKIs are for patients who have intercranial metastases. I do want to point out, however, there was a retrospective study done. It was an international study, but again retrospective in nature, that it did demonstrate that cabozantinib [Cabometyx] does have activity in patients with intercranial metastases, but again I caution that it’s retrospective and it’s unclear if that’s something that’s limited to cabozantinib, although the retrospective study was done for patients who were receiving cabozantinib. I just want to move to the bone metastases patients as well. We know this tends to portend maybe a poor prognosis in patients. It’s a little bit more challenging again to measure bone metastases and to measure responses.

That said, 2 of the combinations have published really robust data from their trials; the CLEAR trial for lenvatinib [Lenvima] and pembrolizumab and the CheckMate 9ER trial with cabozantinib and nivolumab, and both demonstrate that the combination of cabo/nivo or lenvatinib and pembrolizumab both have activity in patients who have bone metastases as well. I do think either of those combinations is reasonable to use and that is based on prospective data. Again, it’s subgroup analyses but at least there is clear data in the trials of len/pem, lenvatinib and pembrolizumab, and cabozatinib and nivolumab in patients who have bone metastases.

Tian Zhang, MD: Perfect. Thanks so much, Moshe, for that approach.

This transcript has been edited for clarity.

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