ASCO GU 2017: Optimal Selection of Front-Line Therapies for Metastatic Renal Cell Carcinoma - Session Highlights
The historic significance of IL-2 cannot be overstated, she observed. It was the first, and for a long time only, agent approved for MRCC, and the agent provided sustained remission for more than 10 years in a small subset of patients. An attempt at dose reduction to make it more tolerable failed, unfortunately, so unless a patient can be treated with high-dose IL-2, he or she should not receive it. Evidence suggests that in the targeted era, there is still a role for IL-2 in attempting remission in certain patients. The ongoing PROCLAIM Trial shows that IL-2 consistently demonstrates a 15% complete or partial response rate in those under the current treatment paradigm. Hence, even patients who received prior targeted therapy could still achieve remission with IL-2 therapy.
There is a preponderance of data that led to the approval of vascular endothelial growth factor and tyrosine kinase inhibitors as front-line therapy in MRCC, starting in 2005. Comparisons of antiangiogenic treatments against one another have failed to demonstrate any major breakthroughs. For example, in the COMPARZ Trial of pazopanib vs. sunitinib, there was no significant difference in objective response rate or overall survival. More recently, however, the CABOSUN T rial of cabozantinib (cabo) vs. sunitinib appears to show that cabo in intermediate- and poor-risk groups of patients might demonstrate improved efficacy over sunitinib. In subgroup analyses, individuals with bony metastases appear to achieve the most benefit. This is important because it is the first time that any agent has demonstrated consistently superior efficacy compared with sunitinib.
Now that immune therapy is blossoming with the development of immune-checkpoint inhibitors, we can study immune therapy combined with targeted therapy. Indeed, many immune therapies are already showing excellent activity in this space. For example, the Checkmate 016 study of nivolumab + ipilumumab has demonstrated a 53% progression-free survival at 6 months. Completed results are still pending. Combination bevacizumab + atezolizumab has shown promising results in phase-II trials and is currently under investigation in phase-III randomized patients. Several similar trials in this space are under accrual, and Dr. Vaishampayan noted that we are anxiously awaiting the results.
Clinicians and researchers must evaluate the risk/reward ratio of these new agents and combinations of agents. Better short- and long-term goals should be established to help organize results of ongoing trials and to standardize reporting of outcomes. Although treatment for patients with MRCC has so far been empirically targeted against clinical markers, the growing availability of biomarkers may help improve treatment strategies in a biologically meaningful way.
This is an exciting time for the discovery of drugs in the battle against mRCC, she concluded. The incipient field of immune-targeted therapy has the great promise to revolutionize front-line MRCC treatments. With the multitude of ongoing trials, hopefully we should get the answers to many important questions in the near future.
Speaker: Ulka N. Vaishampayan, MD; Karmanos Cancer Institute, Wayne State University
Written By: Shreyas Joshi, MD, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA