San Antonio, Texas USA (UroToday.com) Dr. Jonasch and Dr. Choueiri presented topics regarding the appropriate identification of tumor targets in aggressive and metastatic RCC. There have been impressive new gains in the field with the identification of PD1/PDL1 checkpoint inhibitors, but the overall response rate is still not as high as we would hope; indeed, more people don’t respond to therapy than do respond.
Clearly, there is room for improvement in this space, and the future will likely belong with combinations of therapies. There are several current trials studying just this, the most promising of which are combining checkpoint inhibitors with mTOR, TKI, or VEGF inhibitors. Furthermore, most therapeutic data is only relevant in the clear cell RCC (ccRCC) population, and researchers are still working to identify active agents against non-ccRCC tumors. Lastly, with data from the S-TRAC and ASSURE trials recently published, the role of adjuvant therapy in high-risk localized RCC is up for continued debate.
The panel question/answer session discussed these and other topics regarding the future of targeted therapies in high-risk kidney cancers.
Queston 1: What should we be prioritizing in terms of therapy and outcome, and what study or studies should we be doing?
The panelists discussed the need for more information from Phase II studies currently underway, especially for combination therapies that can help determine the path forward. There needs to be an appreciation that tumor microenvironments differ, and attention should be paid to identifying these differences when developing trials in the future. Dr. Choueiri made a poignant point: Research focuses a great deal of attention to biomarkers of disease progression and treatment effect, but many of these biomarkers are related to a single therapy. Combination therapies may make these same biomarkers clinically irrelevant, as the mechanisms of action of combination therapies may be quite different. Ideally, treatment responses would be so good that biomarkers won’t matter as much, but we have not reached that point yet.
Question 2: Is everolimus still a useful drug in these patients?
Despite the massive influx of new drugs in this space, the panelists still believe that everolimus is a safe and clean drug, and we are able to manage its toxicities well. We should continue to utilize this in the appropriate patients.
Question 3: How should we be counseling patients on the merits or adjuvant therapy for high-risk localized RCC?
We still don’t have a clear answer on the impact of adjuvant therapy. The S-TRAC and ASSURE trials give us differing results, but the S-TRAC data does give us some encouragement that there is a benefit to adjuvantly treating high-risk patients. However, it should be noted that patients with nonmetastatic high-risk disease generally have a lower tolerance for side-effects than patients with metastatic disease. Therefore, the considerable toxicity profiles of these drugs makes adherence tricky, and we should focus on treatment combinations that improve outcomes without multiplying toxicities.
There is also some evidence that there may be racial differences in response rates. This has not been fully evaluated yet and may be a promising area for future research.
Question #4: Where should we be heading after S-TRAC?
The panelists discussed that we should be very deliberate in how we move forward in the adjuvant therapy space. We should insure that adjuvant therapy is actually changing the biology of disease rather than just prolonging disease-free survival in exchange for toxicity.
Presented By: Allan Pantuck, Toni Choueiri, Surena Matin, Adam Metwalli
Written By: Shreyas Joshi, MD, Fox Chase Cancer Center
17th Annual Meeting of the Society of Urologic Oncology - November 30 -December 2, 2016 – San Antonio, Texas USA