Several questions remain unanswered regarding the PD-1 blockade based pathway, including patient selection, overcoming innate acquired resistance through combination therapy, and if toxicities will limit potential. As tumors use complex, overlapping mechanisms to evade and suppress the immune system, there is much potential in shifting the balance toward anti-cancer immunity with combined VEGF/PD-L1 blockade.
The IMmotion 150 phase 2 trial examined first line treatment of Atezolizumab and Bevacizumab vs. Atezolizumab alone vs. Sunitinib alone. This study showed encouraging efficacy by progression free survival (PFS) when treated with the combination (Atezolizumab +Bevacizumab) when compared to Sunitinib. Furthermore, this treatment combination demonstrated improved PFS vs. Sunitinib in the T-effector (HIGH) subset. One of the proposed goals is to identify predictive biomarkers of response to Atezolizumab/Bevacizumab combination therapy and also identify biomarkers of progression and mechanisms of resistance.
The S-TRAC study, examining adjuvant Sunitinib in high risk RCC patients, was a randomized, double blinded, placebo controlled phase 3 trial with disease free survival (DFS) as its primary endpoint. The study showed a clear advantage for Sunitinib in DFS. However, no overall survival benefit was noted, although results were probably still preliminary. The question arises whether we should be using TKIs at this point, or is there a better way.
Dr. McDermott concluded his presentation, stating that there is conflicting data from ASSURE and S-TRAC studies regarding the role of adjuvant treatment, but the net result favors observation and not treatment. The future will probably involve adjuvant immunotherapy and enrollment of patients into clinical trials is required.
Presented by: David F. McDermott, MD
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 18th Annual Meeting of the Society of Urologic Oncology, November 29-December 1, 2017 – Washington, DC