First line targeted therapies include sunitinib, pazopanib, temsirolimus, axitinib and bevacizumab/interferon. Sunitinib and pazopanib are the preferred drugs in the 1st line therapy for metastatic RCC (mRCC). The COMPARZ trial compared pazopanib and sunitinib in clear cell MRCC, showing that pazopanib is not inferior to sunitinib, and that sunitinib has more side effects. In order to overcome the toxicity profile of Sunitinib, a personalized dosing approach of this drug is entirely feasible.
2nd line targeted therapies include Cabozantinib, axitinib, lenvatinib/everolimus, and everolimus. Cabozantinib is the first targeted therapy to demonstrate an overall survival benefit in mRCC.
Dr. Kim gave his recommendations on usage of targeted treatments. He begins with careful titration of sunitinib, moves on to Nivolumab, Cabozantinib (with careful dose titration for toxicity), and finally uses axitinib.
Up to 40% of patients with locoregional disease relapse following surgery. This has led to adjuvant clinical trials in RCC. These included the ASSURE trial, comparing sunitinib to sorafenib to placebo in the adjuvant setting. Unfortunately neither drugs led to improvement over placebo in disease free survival (DFS), and overall survival (OS). This lead to the conclusion that there is no role for adjuvant VEGFR- targeting TKI therapy in adjuvant RCC. Other similar studies have arisen since, including the S-TRAC study, randomizing patients to either sunitinib or placebo, in the adjuvant setting. This trial was to first to report significant clinical benefit of any adjuvant therapy in RCC.
Another trial was PROTECT, comparing placebo to pazopanib for a year, in the adjuvant setting. This was a negative study without any significant difference in OS and DFS in both groups.
Dr. Kim finally focused on non-clear cell RCC, representing 15-25% of all primary renal malignancies. These generally do worse than clear cell RCC in their response to targeted therapies. Available treatments have a modest effect for papillary RCC (pRCC). Current undergoing randomized trials are analyzing the effect of several targeted therapies in pRCC.
Dr. Kim concluded his presentation by sharing his thoughts on the future of targeted therapies in RCC. According to him, the future will mainly focus on the role immune checkpoint inhibitors (ICPI) will have with VEGF targeted therapies. Additionally, finding accurate biomarkers will enable us to treat the right patients with the right drugs.
Presented By: Won Kim, MD, University of California, San Francisco Medical Center
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
at the 2017 Bladder Cancer Academy - June 9 - 10 - Schaumburg, Illinois, USA