Ulka Vaishampayan, MD: Can we discuss some of the phase III trials, or the phase III data that have been acquired with both immunotherapy as well as anti-VEGF therapy as second-line therapies? Rana?

Rana R. McKay, MD: Yeah, certainly. I think the most robust data that we have largely comes from 2 trials. The METEOR trial compared the cabozantinib versus everolimus in patients who had previously been treated with a VEGF inhibitor. This trial demonstrated improvements in objective response, PFS [progression-free survival], and OS [overall response] with cabozantinib over everolimus.

Additionally, we have data from CheckMate 025, which has looked at nivolumab alone compared with everolimus post-VEGF inhibition. Five-year overall survival data were actually presented by Dr Robert Motzer at GU ASCO [Genitourinary Cancers Symposium] just a couple of weeks ago. It’s exciting to see that 26% of patients, or about a quarter of patients who received nivolumab, were alive at 5 years out from receipt of that therapy. It’s really encouraging to see that long-term data.

The issue with both of these studies is that obviously they’re done post-VEGF inhibition. We don’t really have data regarding post-I/O [immuno-oncology], as to what’s the best sequence and best agent to use after an immune checkpoint inhibitor. We’re lacking in that, and this is where real-world data really come in handy.

Ulka Vaishampayan, MD: Yes. The real-world data are definitely valuable, especially since we don’t have prospective trials yet for post-I/O therapy. Asim, do you want to take us through the real-world data that were presented?

Mehmet Asim Bilen, MD: Yeah. I agree with you, although I wish we had prospective data with every single combination and every single sequence. That is practically impossible. Because of this reason, we have to rely on real-world data, knowing that all the retrospective studies carry over some different biases.

There were a couple of abstracts presented as posters at GU ASCO 2020. Dr Igor Stukalin reported on using a second-line VEGF TKI [tyrosine kinase inhibitor] after an immunotherapy-based combination. As we predicted, the VEGF TKI showed activity after immunotherapy-based first-line treatment. Also, the response rates were higher in patients first treated with I/O-I/O versus I/O-VEGF, which actually is expected.

There were also a number of abstracts presented on the activity of cabozantinib in the relapsed-refractory setting. One of the cohorts reported real-world evidence of cabozantinib as effective, and the data are very comparable with the METEOR trial. And so this is a valid option for using as treatment in the relapsed-refractory setting.

There was also another abstract presented at GU ASCO 2020 that looked at activity of cabozantinib from first-line therapy through fourth-line therapy. They showed the response rate and time to therapy failure is maintaining from first line to the fourth line, which is quite encouraging. Sometimes we want to use those drugs as early as possible, but if the agent is still active in the second-line, third-line, or even fourth-line setting, this really impacts the outcome of the patients we treat in our clinic.

Overall, after I/O-based therapy, VEGF is the way to go for second-line therapy. This can be cabozantinib, or Lenvima [lenvatinib] plus everolimus. Either is a good option that we can use in our clinic.

Ulka Vaishampayan, MD: I agree with you. Cabozantinib definitely seems to have activity post I/O as well as post VEGF TKI.

Transcript Edited for Clarity