Daniel George, MD: Hello, and thank you for joining this OncLive® Peer Exchange® titled “Evolving Treatment Paradigms for Renal Cell Carcinoma.” The standard of care for patients with metastatic renal cell carcinoma continues to change rapidly as novel therapies and combinations have gained recent FDA approval. The busy oncologist treating a patient with metastatic disease now has a plethora of choices for both newly diagnosed and relapsed kidney cancer. In this OncLive® Peer Exchange®, my colleagues and I will look at the challenges in finding the right systemic treatment for the right patient. We’ll talk about the data from the ASCO 2018 Annual Meeting and how it relates to the treatment of advanced disease.
I am Dr. Daniel George, and I serve as director of Genitourinary Oncology at the Duke Cancer Institute in Durham, North Carolina. Participating today on our distinguished panel are Dr. Robert Amato, professor of oncology at UT Health McGovern Medical School and chief of the Division of Oncology at the Memorial Hermann Cancer Center in Houston, Texas; Dr. Toni Choueiri, of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School in Boston, Massachusetts; Dr. Richard Joseph, assistant professor of oncology, Division of Hematology/Oncology, at the Mayo Clinic in Jacksonville, Florida; and finally Dr. Walter Stadler, professor and chief of Hematology/Oncology in the Department of Medicine at the University of Chicago in Illinois. Thank you so much for joining us. Let’s begin.
Starting out, gentlemen, within newly diagnosed metastatic renal cell carcinoma, there have been a couple of new approvals this past year now for the treatment. Toni, do you want to walk us through cabozantinib and the CABOSUN data and how they have led to its new approval?
Toni Choueiri, MD: Absolutely, Dan. We launched with Alliance and the National Cancer Institute, a randomized phase II study, to ask whether cabozantinib is superior to sunitinib, a long-standing standard of care in renal cell carcinoma. The premise is that cabozantinib targets VEGF receptors and other receptors involved in resistance to VEGF inhibitors. We focused on an intermediate and poor population, with the primary endpoint of PFS. Progression-free survival was met by both investigator assessment and independent review, and based on that, cabozantinib was approved by the FDA as an option for untreated patients.
Daniel George, MD: Talk a little bit about that approval. It was a little bit broader than what the actual study looked at.
Toni Choueiri, MD: Correct. We see that approval differed sometimes from the FDA to the European agencies. It was approved on all risk groups by the evidence that CABOSUN data did not include patients with good risk and, essentially, these patients with a clear cell component. There are emerging data in patients with non—clear cell component, and I think the train has left the station because cabozantinib is now being explored in combination with other drugs, including immune checkpoint inhibitors, like our planned study again from Alliance.
Daniel George, MD: We’re going to get to that, but Walt, I want you to weigh in here. The CABOSUN data and the new approval of cabozantinib: Does that change your practice in frontline metastatic RCC?
Walter Stadler, MD: I think it does a little bit; it becomes, for me, another option. Although, we have to recognize that this was a randomized phase II study, with a progression-free survival as an endpoint and not an overall survival endpoint. We see some improvements in progression-free survival. Whether that actually translates into overall survival is unknown. It is a reasonable intermediate endpoint but not a perfect intermediate endpoint. I have a little bit of concern with the broad approval for all prognostic groups because this trial did not include patients with good-prognosis disease. We have to keep in mind issues of toxicity where we have, for example, a trial that compared pazopanib versus sunitinib, in which there was an improvement in tolerability in the pazopanib group across a broader range of patients.
Daniel George, MD: Fair enough. Efficacy versus tolerability. It’s a balance, right?
Walter Stadler, MD: Correct.
Daniel George, MD: We’re going to weigh both of those, particularly depending on the patient population we’re looking at, and we’re going to get into patient selection in a little bit. Any thought, Rich, from your perspective on—and I know you’re newer to the field in this field, but sometimes fresh eyes give a new perspective. What are your thoughts on CABOSUN, and have you used that in the frontline setting?
Richard W. Joseph, MD: I think cabozantinib is a very great drug. Beating out sunitinib with PFS at least shows us that it has at least equivalent, if not better, activity in those groups of patients. I do agree with Walt, that the toxicity for me, in my hands does seem to be a bit worse, especially at the initial dose of 60 mg. I tend to start patients at a lower dose, and I think certainly building off that from the COMPARZ study, it probably is more toxic than Votrient as well.
Transcript Edited for Clarity