AUA 2019: How Are We Improving Outcomes of Locally Advanced RCC?
Dr. Karam began the discussion by discussing the history of tyrosine kinase inhibitor (TKI) therapy. We traditionally have used TKIs in order to decrease tumor size and reviewed the prior trials showing that there does appear to be efficacy in reducing tumor size. The next use for TKI therapy is changing unresectable disease to resectable disease and reviewed the clinical trials showing mixed results for this use. Next, we also have used TKIs to change a tumor that would require a radical nephrectomy to partial nephrectomy. He again showed that there was mixed data for this use in the TKI-era. Finally, he discussed that while TKI use has been tried to decrease IVC tumor thrombus volume, there is minimal data to support this use. He then reviewed some of the TKI or immunotherapy (IO) trials that are continuing to accrue Dr. Karam concluded that we need to better define which drug or drug combinations are optimal in treating advanced RCC. Furthermore, we need to determine if these drugs work best in the neoadjuvant setting prior to nephrectomy or in the adjuvant setting. Finally, he concluded that it is crucial that we begin to evaluate survival endpoints for these patients in future studies.
Dr. Maranchie then took the podium and began by defining the goal of adjuvant therapy which is to reduce a “statistical risk” of relapse due to residual disease. She noted that up to $40 of intermediate and high-risk renal cell carcinoma (RCC) patients will relapse after surgery and that the median survival from diagnosis of metastatic disease to death in the targeted therapy era was 28-29 months. Dr. Maranchie then reviewed several of the adjuvant targeted therapy trials over the last 12 years, including ASSURE, S-TRAC, PROTECT, ATLAS and reviewed the trial design and findings. She summarized that none of these trials, other than S-TRAC showed a benefit for disease-free survival and that none of them, unfortunately, showed a benefit in overall survival. She noted that fortunately immunotherapy has come along and reinvigorated our interest in adjuvant trials for high-risk RCC. She reviewed the PD-1 / PDL-1 pathway as well as the CTLA-4 pathway and discussed how checkpoint inhibitors help the immune system overcome the immune evasion that often occurs in cancer cells. Next, Maranchie reviewed the adjuvant immunotherapy trials which are accruing, including IMMotion 210, randomizing high-risk patients to atezolizumab versus placebo, KEYNOTE 564, randomizing patients to pembrolizumab or placebo, CHECKMATE 914, randomizing patients to ipilimumab and nivolumab or placebo, RAMPART, randomizing patients to durvalumab, durvalumab plus tremelimumab, or observation, and EA8143: PROSPER, which will evaluate checkpoint inhibitors in the neoadjuvant setting.
Dr. Maranchie concluded that these upcoming trial results will hopefully show efficacy and will offer us new options for treating patients in the adjuvant space for patients with advanced RCC
Presented by: Jose Karam, MD, MD Anderson Cancer Center, Houston, Texas and Jodie Maranchie, MD, University of Pittsburgh Medical Center, Pittsburgh, PA
Written by: Brian Kadow, MD. Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA. @btkmduro at the American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois