COSMIC-021: Cabozantinib plus atezolizumab gives encouraging clinical activity in inoperable locally advanced/metastatic urothelial carcinoma

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Published: 5 Jun 2022
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Dr Sumanta K. Pal - City of Hope Comprehensive Cancer Center, Duarte, USA

Dr Sumanta K. Pal speaks to ecancer about the results from Cohorts 3, 4, 5 of the COSMIC-021 study.

Cabozantinib plus atezolizumab demonstrated encouraging clinical activity with manageable toxicity in inoperable locally advanced/metastatic UC as first-line systemic therapy in cisplatin-based chemo eligible/ineligible patients and as second- or later line in patients who received prior immune checkpoint inhibitors.

He concludes by explaining the results of the study and the next steps in the investigation.

The trial COSMIC-021 is one that actually includes multiple histologies across multiple cohorts

including breast cancer, prostate cancer, colorectal cancer. Specifically at ASCO 2022 we presented

data pertaining to urothelial cancer. The study specifically investigated three cohorts of patients –

patients who were cisplatin eligible, cisplatin ineligible and patients who had received prior immune

checkpoint inhibitors in cohorts 3, 4 and 5 respectively. We assessed the combination of cabozantinib

with atezolizumab; cabozantinib was dosed at 40mg daily, atezolizumab at the conventional dose of

1,200mg intravenous every three weeks. Essentially we used objective response rate as the primary

endpoint of the trial. Each cohort, 3, 4 and 5 had thirty patients a piece.


Ultimately we saw a graded response across the three cohorts. Cohort 3, which included a total of

thirty patients had a response rate of 20%; again that was patients that were cisplatin ineligible.

Cohort 4, patients that were cisplatin eligible, demonstrated a response rate of 30%. Finally, in cohort

5 where we had patients with prior immune checkpoint inhibitor therapy we saw a response rate of

10%. Now, one thing that the response rates may not convey is the duration of response and, in

particular, in cohort 4, cisplatin eligible patients, we saw a very healthy duration of response, in fact,

the median value not yet reached. To me, that’s a signal that that’s a particular place where it may

confer some benefit.


Response rates were measured by the investigator, in this case using RECIST version 1.1. Ultimately

the response rates that we saw in COSMIC-021 were encouraging and I would propose that the next

step is already in play in some respects. There’s a trial that’s ongoing known as the MAIN-CAV study

run by Dr Shilpa Gupta at the Cleveland Clinic; it’s being run through the Alliance Cooperative Group.

The trial looks at the principle of using maintenance avelumab with or without cabozantinib, so a

different immune checkpoint inhibitor but the same principle of combining with a multi-kinase inhibitor,

cabozantinib. That’s going to be the ultimate demonstration of whether or not there’s real synergy

between cabozantinib and atezolizumab.


The toxicity profile associated with cabozantinib with atezolizumab in COSMIC-021 was no different

from what we’ve reported out from other cohorts. In general the standouts for toxicity included fatigue,

increases in AST and ALT and so forth, but in most cases the toxicities were quite manageable.

Importantly, we didn’t see any grade 5 adverse events in the study.