Sequencing for Metastatic Clear Cell Renal Cell Carcinoma After Prior Therapy

Lenvatinib/Everolimus Vs Tivozanib Evaluated for Later-Line RCC

Benjamin Garmezy, MD, discusses the choice of third-line therapies in patients with advanced renal cell carcinoma.

Benjamin Garmezy, MD, assistant director of genitourinary research at Sarah Cannon Research Institute and genitourinary medical oncologist at Tennessee Oncology, discusses the choice of third-line therapies in patients with advanced renal cell carcinoma (RCC).

According to Garmezy, oncologists may choose between tivozanib (Fotivda) and the combination of lenvatinib (Lenvima) and everolimus (Afinitor). Based on tivozanib’s efficacy as well as its favorable tolerability and quality-of-life data versus sorafenib (Nexavar), he says it would be a good choice for patients whose performance status is an issue. Tivozanib was investigated in patients with RCC who were more heavily pretreated, and many had received prior immunotherapy, which is more representative of the real-world population who now frequently receive frontline immune checkpoint inhibitor therapy.

Lenvatinib/everolimus may be appropriate for patients who are able to tolerate it and who may benefit from the addition of everolimus, an mTOR inhibitor, to a tyrosine kinase inhibitor. Garmezy says that these agents have not been compared head-to-head, but the performance status or disease volume may influence decision making. Additionally, he notes that tivozanib is still an option if a patient’s disease progresses after receiving lenvatinib/everolimus.

TRANSCRIPTION:

0:08 | [Tivozanib] therapy versus lenvatinib and everolimus—I feel like that's generally how this clinical question is going to come up. And so what I would say is first, for any patient that you are concerned about from a performance status standpoint, tivozanib is a good choice. It's well tolerated [and] it has strong level 1 evidence for its use in a refractory setting. The patients in the TiVo-3 trial were more heavily pretreated than the patients in that phase 2 lenvatinib/everolimus trial. These were patients in the third and fourth line compared [with those] mostly in the second line. And also these patients had received prior immune therapy…some of them have, which is more similar to a current real-world patient [for whom] an oncologist has to make a decision for in the clinic.

0:49 | All that being said, there are those patients who giving lenvatinib/everolimus to also makes a ton of sense; patients who you think can tolerate it; patients who you think could use that additional therapeutic class with the mTOR inhibitor. So it is a tough decision. I do think the quality of life probably tilts a bit into tivozanib's favor. And then for patients that you're looking to give a stronger punch, perhaps with an mTOR inhibitor as well I think lenvatinib/everolimus is reasonable though we can't say it's better. These 2—obviously these therapeutic regimens have not been compared head-to-head, though you could also consider sequencing tivozanib even after that doublet as well if you need to.