Medicine Matters oncology

So my name is David McDermott. I'm a medical oncologist in Boston at Beth Israel Deaconess Medical Center, and I focus on treating kidney cancer and melanoma.

At this meeting, we were focused on a new target in kidney cancer called CXCR4, which we believe is involved in resistance to both angiogenesis inhibition and immune therapy, potentially. So we presented a trial, a Phase II trial, single-arm trial of axitinib, which is a standard therapy for kidney cancer, with this new agent mavorixafor, which is an inhibitor of CXCR4. We believe CXCR4 is important because we believe it's important in allowing cells like myeloid-derived suppressor cells and T-regulatory cells to track into the tumor where they generate resistance to both-- they support resistance to both angiogenesis inhibition and immune therapy.

So in this trial, adding this drug to axitinib produced some encouraging results. So for example, we saw a very good tolerability, meaning the side effects we saw were mostly driven by the axitinib. We saw some encouraging early signs of efficacy in about 60 patients. We saw a progression-free survival for the entire group of about 7.4 months, which is better than the historical number you'd see with axitinib alone of just 4.8 months. Obviously, we need to confirm that in a randomized trial. But the drug is interesting and it may also be able to be combined with PD-1 blockades.

So as part of this study, we had a small cohort with combined with nivolumab. So now this agent has been combined with both PD-1 and with VEGF with some interesting results. So it's one of the few drugs in development that's been combined with both sides of the current standard of care for patients with metastatic kidney cancer. One of those standards is PD-1/VEGF. So you could imagine a drug like this potentially being added to a triplet combination in the future, as well as doing randomized trials in patients who are just receiving VEGF alone. So we're excited about that going forward. More studies are needed, obviously.

The other thing that we talked about at this meeting was a novel endpoint for immune therapy trials, this what we're terming treatment-free survival, which is a way of looking at overall survival of patients on therapy and off therapy and on subsequent therapy. It's a way of sort of breaking down survival, the different stages people would be in while they're alive. They can either be alive on treatment, they can be alive on subsequent treatment. But with immune therapy, one of the exciting aspects of immune therapy is you can be alive off treatment and living in remission of your disease.

So treatment-free survival is a way of measuring that outcome. But not just looking at the positives, not just looking at the treatment-free intervals people get, but also the toxicity that may persist during that period, because both the positive effects of immune therapy can last for months, and, in some patients, years, but also, side effects can last, too. So we were showing both toxicity and benefit during this period.

And we looked at it in the CheckMate 214 study, which was the pivotal trial that led to ipilimumab and nivolumab being approved for use. And there we saw much more treatment-free survival in the patients getting IO therapy than sunitinib without a subsequent increase in side effects. So this might be a way of-- additional way-- on top of progression-free survival and overall survival, about measuring the true value of immune therapy in patients getting combination regimens in the future.

We published this data two weeks ago in melanoma. This was the first look in kidney cancer. And we hope to look at it in other tumor types, like lung cancer, in the near future.