Therapeutic Advances and Key Case Studies in RCC - Episode 12
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In the oncology setting, the inhibition of PD-1 has proven to result in the body’s recruitment of a strong immune response against tumor cells. The most developed compound of this class, notes Daniel Heng, MD, is nivolumab, where ongoing phase 1, 2, and 3 studies have shown encouraging outcomes. Brian Rini, MD, comments on the results of a phase 2 dose finding study that examined nivolumab in the treatment of renal cell carcinoma (RCC). Response rates were around 20%, and progression free survival was approximately 3 to 4 months.
Rini notes that while overall survival was reportedly extended, there was no control arm in this study, and as such, individuals who made it through second, third, and fourth-line kidney cancer were able to do so because their disease is slow growing. Despite this shortcoming, Rini acknowledges that immune checkpoint inhibitors, such as nivolumab, are active in RCC. Heng lists other hopeful candidates in the RCC pipeline, such as nivolumab in combination with ipilimumab, a dendritic cell vaccine known as AGS003, and cabozantinib, an oral MET inhibitor whose efficacy is currently being compared against everolimus in second-line RCC.
When assessing the effectiveness of these new agents, Rini comments that overall survival should be the primary endpoint. Progression free survival may be interesting to look at, but results from clinical data thus far, particularly those of nivolumab, are not robust enough to warrant approval by the FDA. Comparing overall survival, however, can be challenging due to the large number of active compounds at the moment. While agents used in prostate cancer, such as abiraterone and enzalutamide, have shown improved overall survival in clinical trials, overall survival could not be demonstrated with tyrosine kinase inhibitors (TKIs) because there were too many active drugs and several lines of therapy.
Rini speculates that kidney cancer has received some more latitude in this regard because there was essentially nothing prior to the availability of TKI therapies. Rini predicts that this convention of overlooking overall survival will change, however, and future RCC trial designs will need to be able to demonstrate benefit from this perspective.