Sumanta K. Pal, MD, on Urothelial Carcinoma: New Results on Cabozantinib Plus Atezolizumab

The COSMIC-021 study is a trial that includes multiple different histologies, multiple different cohorts. At this year's ASCO meeting, ASCO 2022, I presented data pertaining to cohorts three, four, and five. This specifically looked at patients with advanced urothelial carcinoma. The composition of each of the cohorts was distinct. In cohort three, we had patients that were cisplatin-ineligible. In cohort four, patients that were cisplatin-eligible. And finally, in cohort five, patients that had received prior immune checkpoint inhibitors. What ultimately it boiled down to is about 30 patients per cohort. In terms of the distribution of patients, it was predominantly male, as you might expect. Most of the patients had a bladder primary, although we did actually have good representation of upper track tumors, ureteral tumors, and so forth. That was about 30% of the study population. Amongst those patients that had received prior immune checkpoint inhibitors, about 30% had received one prior therapy implying immune-based treatment, and about 68% had received two or more prior lines of treatment. What we saw was actually a graded response. In patients who were cisplatin-eligible we saw the highest response rate, 30%. In patients that cisplatin-ineligible we saw a response rate of 20%. And finally, in patients that had received prior immune checkpoint inhibitors, we saw a response rate of 10%. It's always tricky to know what endpoints to follow in these relatively small studies. One thing that really I found intriguing was the duration of response. And with substantial follow up at this point in time, we still haven't reached the median duration of response amongst those patients that were cisplatin-eligible. I really think that the toxicity profile that we saw in this study really mimics what we've seen in other experiences of cabozantinib with atezolizumab. The combination seems to be very well tolerated. We used a dose of cabozantinib at 40 milligrams. The rates of hepatitis, the rates of other toxicities that you'd expect with a combination like diarrhea, were very reasonable and manageable by and large. So in summary, I think that this combination really does have activity. My hope is that we'll be able to study it further in certain contexts. And in particular, there's a study ongoing right now that I'll plug, MAIN-CAV through the Alliance. It's led by Dr. Shilpa Gupta. This trial I think is a prime way for us to understand the role of cabozantinib with immunotherapy where that combination's being assessed in the maintenance setting.