Neoadjuvant Cabozantinib Enables Resection of Advanced RCC If Timed Properly

Naomi B. Haas, MD, discusses the use of VEGF tyrosine kinase inhibitors as neoadjuvant therapy for renal cell carcinoma.

Naomi B. Haas, MD, medical oncologist, director of the prostate and kidney cancer program, and professor of medicine at the Hospital of the University of Pennsylvania, discusses the use of VEGF tyrosine kinase inhibitors (TKIs) as neoadjuvant therapy for renal cell carcinoma (RCC).

TKIs that target VEGF, including cabozantinib (Cabometyx), are currently being explored in the adjuvant and neoadjuvant setting in RCC. A phase 2 study (NCT04022343) of neoadjuvant cabozantinib from Emory University showed its capability to shrink renal cell tumors to enable surgical resection.

According to Haas, a challenge for this approach is that VEGF TKIs can interfere with wound healing, potentially complicating surgical resection and recovery. However, she suggests that this effect can be managed by ending administration of cabozantinib before surgery based on the drug’s 5-day half-life, but not early enough to allow tumor regrowth.

Other studies have shown that this procedure is possible, Haas says. The phase 2 study reported that no surgical complications related to cabozantinib occurred in 15 patients who received surgery.


0:08 | A number of VEGF TKI approaches have been taken in the neoadjuvant setting. The general approach has been…given that cabozantinib is 1 of the VEGF TKIs that is thought to be 1 of the most active in RCC—the idea has been with this kind of approach, if it can be administered in a safe way and achieve as much tumor shrinkage as possible.

And one of the challenges with VEGF receptor TKIs in the neoadjuvant setting has been that they interfere with wound healing to some extent. Cabozantinib has a half-life of about 5 days. So, the timing of it has to be such that it can be administered and then allow enough time to stop where the patient can safely proceed with surgery, but also not be off the drugs so much that you get a rebound effect. And I think we've seen with other trials, that is indeed possible.