Medicine Matters oncology

I presented data at ASCO this year about tivozanib, specifically a post hoc analysis from TIVO-3, which was a trial that looked at tivozanib versus sorafenib in a refractory setting. Patients had gotten two or more prior systemic treatments. I've heard people say that if a patient progresses through a very VEGF receptor-targeted therapy, so one that's very selective against the receptor such as axitinib, that they really need to go on a multi-targeted therapy, because if you give them another very selective therapy that they won't respond.

And so we could look at this in TIVO-3 by looking back at all the patients who had gotten prior axitinib. So axitinib and tivozanib are fairly biochemically similar in the sense that they both hit the VEGF receptor, and they don't hit much else. So they're very selective. And so we looked at a number of patients who had gotten prior axitinib which is now very much part of the front line standard of care in kidney cancer with the combination of pembrolizumab and axitinib. And we looked at how they did on TIVO-3, that is, if they got subsequent tivozanib or if they got subsequent sorafenib. And the top-line results are that in that subset the results were similar as the intent to treat population or similar as patients who didn't get prior axitinib meaning there was a progression free survival advantage and a response rate advantage as well. And the tolerability was about the same as the general population.

So it really refutes that notion that if you get a selective VEGF inhibitor, you have to go to something multi targeted. In fact in this case, the selective TKI, that is, tivozanib was more effective than the multi targeted TKI of sorafenib. Now, sorafenib is not really in common use anymore. Other drugs, such as cabozantinib and now lenvatinib, et cetera, which are multi-targeted, would be more likely in use, but it was just the one chosen for that trial. So I think it at least provides some data for clinicians to know that they have some flexibility when choosing TKI. Tivozanib's not approved in the US yet, but when it is obvious it will allow that flexibility in the refractory setting and some confidence that patients can and do respond to this drug in a refractory setting regardless of prior treatment.

I think it can and will move to earlier lines of therapy. If a patient fails in IO/TKI doublet, in essence they've had two different therapies although they were combined and I think it certainly could be used in that setting. I would say there's more indirect data than direct data but we know TKIs are active in that setting. And again from a tolerability standpoint I think it's the best tolerated TKI.

It's the kind of thing like, it'd be great to have a big trial that compares all the doublets so we could tease out which one is best et cetera, but it's not going to happen. So, whatever my opinion is and I don't know that frankly that's the best use of our resources. Kidney cancer thankfully is a relatively rare disease and so I think we need to be just a little more thoughtful about the resources, human resource and patient resources that we're using, to study questions. And I think the field is better off studying other novel combinations of two drugs of three drugs looking at biomarker based trial design, et cetera, I think that's where our efforts should be spent, to do a trial of axi-pembro versus cabo-nivo versus len-pembro.

Yeah, we'd all love to see the results but I'm not really sure that advances the field. You know, we have big data sets, we can compare although imperfectly across trials. And I might choose regimen A certain reasons and somebody else might choose regimen B and I think that's fine. I think patients are benefiting either way. I don't think there are more similarities than differences. So, while useful practically it won't happen and again frankly I think our efforts are better focused elsewhere.