Impact of CheckMate 9ER on the Treatment of Advanced RCC

Sumanta K. Pal, MD: We’re always looking toward what the best mechanism might be. A lot of the preclinical data suggest that cabozantinib might potentially offer the least resistance when it comes to treating patients with advanced kidney cancer by inhibiting MET and AXL and a multitude of other receptor tyrosine kinases beyond VEGF. The preclinical data suggest that MET and AXL may be bypass mechanisms. Cabozantinib holds a lot of weight from that perspective.

I would suggest that, in terms of the clinical data, when you look at the CheckMate 9ER trial data set, you'll see that a relatively large proportion of patients had their tumors remaining intact: it was about 30% of the population. Those patients tended to fare quite well, which was impressive. I would also say that patients with bony metastases did quite good in the context of the Checkmate 9ER trial. That’s another standout in the data because we see many patients in the clinic with bone metastases. We don't know what to do with them, but we've suspected for a long time that cabozantinib may be better for those individuals. That's where we see cabozantinib with nivolumab standing out among the pack of other available options.

Toni Choueiri, MD: I expect this combination to be a player in the first-line setting for renal cell cancer. It’s also refreshing to see that this is a TKI [tyrosine kinase inhibitor] that was able to be combined with an immune checkpoint blocker. Unfortunately, initial studies using nivolumab with sunitinib or pazopanib showed that it was not able to be combined due to significant toxicities. It was the same for pazopanib: it was not able to be combined with pembrolizumab. These TKIs here, like cabozantinib, were able to be combined. There was another oral presentation and a poster presentation with cabozantinib with another immune checkpoint inhibitor by the name of atezolizumab. It is not approved in renal cell carcinoma, but it is approved in other malignancies. There was significant activity. The study was presented by Dr Pal, Bradley McGregor, [MD,] one in clear cell and the other not in clear cell. Both told us that this combination can be tolerable and the adverse effects manageable. The combination of cabozantinib/atezolizumab is moving to a phase 3 trial in renal cell cancer in the post-IO [immune-oncology] setting.

Transcript Edited for Clarity