In a multicohort phase Ib study (COSMIC-021) reported in the Journal of Clinical Oncology, Sumanta K. Pal, MD, FASCO, and colleagues identified the activity of cabozantinib plus atezolizumab in a cohort of patients with locally advanced or metastatic urothelial carcinoma according to first-line cisplatin eligibility and previous platinum-containing chemotherapy or immune checkpoint inhibitor (ICI) treatment.
Sumanta K. Pal, MD, FASCO
Study Details
In the international trial, 121 patients enrolled between March 2018 and November 2021 received cabozantinib at 40 mg once daily and atezolizumab at 1,200 mg every 3 weeks in four groups:
- First-line cisplatin–eligible patients (cis-eligible, n = 30)
- First-line cisplatin–ineligible patients (cis-ineligible, n = 30)
- Patients with previous treatment with platinum-containing chemotherapy (previous chemotherapy, n = 30)
- Patients with previous ICI treatment (n = 31).
The primary outcome measure of the trial was objective response rate.
Key Findings
Objective response rates were 30% (95% confidence interval [CI] = 15%–49%) in the cis-eligible group, 20% (95% CI = 8%–39%) in the cis-ineligible group, 27% (95% CI = 12%–46%) in the previous chemotherapy group, and 10% (95% CI = 2%–26%) in the previous ICI group. Median progression-free survival was 5.5 months (95% CI = 1.6–11.6 months), 5.6 months (95% 3.1–11.1 months), 5.4 months (95% CI = 1.6–7.6 months), and 3.0 months (95% CI = 1.8–5.5 months) in the four groups, respectively.
Grade 3 or 4 treatment-related adverse events were observed in 43%, 67%, 57%, and 45% of patients in the four groups, respectively. Treatment-related adverse events led to discontinuation of all treatment components in 17%, 13%, 3%, and 19%, respectively. No grade 5 treatment-related adverse events were observed.
The investigators concluded: “The novel combination of cabozantinib plus atezolizumab exhibited clinical activity in advanced [urothelial carcinoma] that is cis-eligible, cis-ineligible, or previously treated with platinum-containing chemotherapy; clinical activity in previous ICI-treated [urothelial carcinoma] was modest. The toxicity profile was consistent with that previously reported for the combination.”
Dr. Pal, of City of Hope Comprehensive Cancer Center, Duarte, California, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Exelixis, Inc (Alameda, California), in partnership with Ipsen (Paris, France) and Takeda (Osaka, Japan). For full disclosures of the study authors, visit ascopubs.org.
