Choosing Among TKIs in Advanced Kidney Cancer

Toni Choueiri, MD:The choice of TKI is getting complicated, especially when you add the level of an immuno-oncology drug and the different PD-1 and PD-L1 inhibitors. But actually, what do the data tell us?

In 2013, there was a large phase III noninferiority trial of pazopanib versus sunitinib, both very similar VEGF receptor inhibitors. That showed that pazopanib was not inferior in terms of activity compared with sunitinib. But in general, if you look at several quality-of-life domains, the drug is better tolerated. So, this drug has been a preferred drug in many settings in the community—and then came cabozantinib. Although it still was not compared to pazopanib, it was compared with sunitinib in the frontline setting and showed superiority, though in a small trial, but has very intriguing activity in bone metastases in patients who were at intermediate and poor risk.

For the frontline space, it is complicated. Pazopanib seems to be as active as, or not inferior to, sunitinib. Also, numerically, the numbers were a bit higher with sunitinib. But it’s not inferior if you look at the whole trial, the statistical consideration—it’s usually better tolerated—and you have a drug that is very active in the second-line setting. In the frontline setting, that seems to be better than sunitinib, at least with response rate and progression-free survival.

I still think that the future is combinations. And while sunitinib and pazopanib were not able to be combined with a checkpoint blocker, like pembrolizumab or nivolumab, due to excess toxicity, cabozantinib so far, at the lower dose of 40 mg a day, was able to be, you know, combined with nivolumab in a study at the NCI, and, hopefully, this regimen actually is progressing the cabozantinib/nivolumab toward a phase III trial.

Transcript edited for clarity.