Initial Therapy for Advanced Renal Cell Carcinoma - Episode 2

Treatment Landscape of Advanced Clear Cell RCC


Eric A. Jonasch, MD: In 2020, choosing frontline therapy for renal cell carcinoma [RCC] really requires us to look at a number of different factors. The first factor is histology, and although we don’t treat people tremendously differently on the basis of histology in 2020, we are recognizing that it will likely result in different outcomes. The second thing is going to be risk stratification. Taking either Memorial Sloan Kettering Cancer Center or IMDC [International Metastatic RCC Database Consortium] risk features, and using those to stratify patients is going to help us very much in deciding which treatment to give patients. The third thing is then going to be tolerability or relative intolerability of immunotherapy. If you have an individual who has an absolute contraindication to checkpoint therapy, that’s going to really change the way you treat patients.

Elizabeth R. Plimack, MD: When I first started in this field, there were really very few agents to try in patients with kidney cancer, they weren’t very effective, and they had a lot of adverse effects. Then the VEGF inhibitors came about, and there were many generations of these, each of which improved somewhat on the other. Trials showed one could work after another had stopped working. And so, VEGF inhibition has been a really key component of treatment of renal cell carcinoma.

One of the drawbacks is that treatment is only effective while the drug is being taken. It doesn’t have durability beyond cessation of the drug. And most patients have some adverse effects from these agents. They have, however, really improved the lives of patients. Patients are living longer and living better as a result of these drugs, whereas before the prognosis for kidney cancer was very poor. Again, these combinations have brought us to yet a new level. Folding immunotherapy combinations into our first-line treatment has raised the percentage of people, for instance, who are alive with metastatic kidney cancer at 2 years. This has gone up from 50% in the VEGF era to over 80% now when we’re looking at combination therapies with VEGF TKIs [tyrosine kinase inhibitors] and immunotherapy.

Eric A. Jonasch, MD: New therapies that we are coming out with now are good from a standpoint of efficacy. But what’s also really important is that these agents are very good from a standpoint of tolerability in general. And one of the deciding factors in which regimen to use in individuals will be whether these agents or combinations of agents are more or less tolerable. So first, understanding what the potential risks or toxicities are of the regimens that you are choosing is very important. And second, understanding how to deal with those once they do occur. Things like taking breaks, dose withholding of antiangiogenic agents, and anticipating immune toxicity all roll in to making the patient’s quality of life better, and ultimately, efficacy, better.

Elizabeth R. Plimack, MD: There are still a lot of unmet needs in metastatic kidney cancer. I think when we’re sitting with a patient and their family and they have a new diagnosis, I would love to be able to one day say to them, “We’re going to treat you and this will be behind you one day, and our goal is to cure you.” I can’t honestly say that yet. I hope that we’ll get there, but the main unmet need is cure of metastatic disease. Second best to cure is long-term control. If we can turn this into a chronic disease that patients are living with on a treatment that they can live and thrive on, then we’ve come close to cure in terms of quality of life and length of life. That’s where I think we can cautiously say we are now with novel VEGF/immunotherapy combinations, and in the patients who have beautiful responses to immunotherapy alone.

We’re starting to see some patients who come off of treatment after being treated with a great response and who are living scan-to-scan off of treatment. But I think it’s just too soon to say how many of those patients there are and whether that’s really a permanent condition where they’re off treatment. But it’s a beautiful thing to see those patients in clinic living and doing well off of therapy. It’s a place I don’t think we thought we would be necessarily. I think we hoped, but we didn’t know for sure. For those patients who really get that benefit, it’s great.

Transcript Edited for Clarity