Insights From: Martin H. Voss, MD, Memorial Sloan Kettering Cancer Center; Thomas Hutson, DO, PharmD, FACP, Baylor University Medical Center; Texas Oncology; James J. Hsieh, MD, PhD, Washington University School of Medicine
Martin H. Voss, MD: We now have 10 targeted therapeutics, FDA approved in the United States, for the treatment of metastatic kidney cancer. So, naturally the question comes up whether or not we need to work on developing more drugs. But there remains a very clear need to developing such drugs. The reason being that despite the wealth of medications we have, the majority of patients will develop acquired resistance or do not respond to these therapies. These are not cured as medications, and the ultimate goal of developing new strategies, including combination regimens, remains to work toward a curative approach in metastatic kidney cancer.
Thomas Hutson, DO, PharmD, FACP: I believe that combination strategies right now appear to be the future for kidney cancer, exploiting now 3 or 4 different pathways, which have shown in clinical trials to be valuable, targetable, and treatable with minimal toxicity and efficacy in our patients. So, combining strategies: VEGF inhibitors with immuno-oncology agents, with mTOR inhibitors, and with FGF inhibitors and c-MET inhibitors—all are potential targets and are valuable and valid combination strategy approaches.
We are seeing now clinical trials move out of the phase I setting of these various strategies. For instance, there are phase I data being reported at ASCO 2017 of cabozantinib combined with I-O therapy. We are seeing phase III trials launching of lenvatinib, which is an FGF VEGF inhibitor, combined with I-O therapy. And there have been completed I-O combination studies with a variety of different VEGF inhibitors, as well as I-O combinations with other I-Os, such as an ipilimumab/nivolumab–type combination.
So, as all these trials finish enrollment, mature, and are presented at future meetings, I’m hoping that we actually do raise the bar and provide amazing benefit to our patients, improving efficacy and tolerability.
Martin H. Voss, MD: We have a growing number of combinations that are being tested, not only in pretreated patients but especially in the first-line space for metastatic kidney cancer. Presently, there are 5 randomized phase III trials ongoing in the first-line space testing combination therapies. Beyond that, we are seeing multiple new combinations being tested in the phase I setting, and we are now actually exploring concepts that are making use of triple combinations—3 medications being given at the same time. So, my impression is that we’re still in the phase where we’re stepping on the gas and trying to see how much harder we can push the envelope.
But I anticipate that at some point, we are going to learn that there are patients who may not need 2 or 3 medications at the same time, and we are also starting to learn that giving more medications at the same time comes at a price—that being toxicity—so it’ll be important in the future to not only test these new combination therapies but also to use rational biomarker development and analyze the data of patients who have already been treated on past trials to understand, Who are the patients who actually need less? Who are the patients we can expose to fewer medications with equal benefit, and who are the ones who actually need these very aggressive approaches with multiple combination cocktails?