Combination Therapies Come of Age in Kidney Cancer

The American Society of Clinical Oncology (ASCO) annual meeting included a kidney cancer session that featured a presentation on combination therapies coming of age in kidney cancer by David A. Braun, MD, PhD, of the Center of Molecular and Cellular Oncology at Yale Cancer Center in New Haven, Connecticut.

In this exclusive MedPage Today video, he discusses the progress that has been made in combination therapies and speculates about what the future holds in this area.

Following is a transcript of his remarks:

This is really a discussion about how kidney cancer therapies, and particularly combination therapies, have come of age. And a discussion of three abstracts — two that are long-term follow-up of what are FDA-approved regimens, standard therapies and immunotherapy, plus an angiogenic molecularly targeted therapy. And one new study where we’re looking at in a second-line setting, a treatment-refractory setting, using again, a re-challenging immune therapy versus just a TKI [tyrosine kinase inhibitor] alone.

And I think both the historical context is important, but also where we’re going. So if we look back over the last 20 to 30 years, it’s been tremendous progress with the development of these combination strategies from a disease where the median overall survival was probably around a year, 20 or 30 years ago, to one where we saw that progress, prolong, and ultimately get to a point where we actually have some patients with long-term durable survival, maybe even cure.

And so that’s really a tremendous development over these last couple of decades, and largely through immune therapy and through combination strategies. And that’s really what the discussion is about. It’s looking backwards, but also looking at where we are now and then looking forward.

I sort of think of this moment as a little bit of a proof of concept — hopefully an inflection point, but certainly a proof of concept that we can get to durable responses. We can really get to cures even in metastatic disease, but it’s not there for enough patients. So how do we go from that proof of concept to making that the norm for most patients with advanced kidney cancer?

And I think there are two broad buckets of strategies in my mind. One is to try to optimize what we have. We have a lot of tools in kidney cancer right now, so how do we sequence things? How do we combine things in ways where we sort of move the ball down the field, where we say, okay, this is not going to be a game changer, but this is going to really in a significant way improve the length or quality of life for our patients. And I think that’s one track that’s really important.

The other track is, I think, a little bit of a reach for the stars, is to say, if we really want to go for cure, we also need some big changes and new ideas. And the space where I think that’s going to happen is in immunotherapy. I think molecularly targeted therapies have been really a tremendous asset in kidney cancer. And they’ve lengthened life, they’ve made quality of life better, but they’re not leading routinely to cures. It’s really the immune therapy component that’s doing that.

So how can we begin to sort of think out of the box in terms of immune therapy beyond just checkpoints. Thinking about other immunomodulatory agents, novel cytokine approaches, even antigen-directive therapies, vaccine-based approaches, and cell therapies — really going to any tool in our immunotherapy tool kit combination to really try to get that ultimate goal of cure for those patients.