Cabozantinib–atezolizumab duo shows urothelial cancer potential in COSMIC-021 study
medwireNews: The combination of cabozantinib and atezolizumab has “encouraging clinical activity” and acceptable tolerability in previously treated patients with advanced urothelial carcinoma, say the COSMIC-021 investigators.
The findings of this cohort of the phase 1b trial were presented in a poster discussion session of the virtual 2020 ASCO Annual Meeting by Sumanta Pal (City of Hope Comprehensive Cancer Center, Duarte, California, USA) on behalf of his co-authors.
“Cabozantinib inhibits receptor tyrosine kinases implicated in tumor growth, angiogenesis, and immune cell regulation, and may promote an immune-permissive tumor microenvironment, resulting in enhanced response to immune-checkpoint inhibitors,” he explained.
Pal added that the multicohort COSMIC-021 study is investigating cabozantinib plus atezolizumab in multiple tumor types, with the current poster focusing on cohort 2 comprising 30 patients who had received prior platinum-based chemotherapy for locally advanced or metastatic urothelial carcinoma.
Treatment with oral cabozantinib 40 mg/day and intravenous atezolizumab 1200 mg every 3 weeks led to an objective response rate (ORR) of 27%, with two complete responses, after a median follow-up of 19.7 months.
Pal highlighted that the median duration of response had not been reached at the time of analysis, and “the longest response [was] ongoing at 15.6 months.”
A further 37% of patients had stable disease, giving a disease control rate of 63%, and the median progression-free survival duration was 5.4 months.
Treatment-related adverse events (TRAEs) of grade 3 or 4 were reported in 57% of participants, with pulmonary embolism the most common event, at 13%, followed by asthenia, at 7%. There were no grade 5 TRAEs.
Twenty-seven percent of patients experienced an immune-related AE of any grade, most commonly hypothyroidism (10%), but there was only one case of a grade 3 event, namely chorioretinitis.
Dose reductions of cabozantinib due to AEs were required by 30% of participants, but no patient discontinued both cabozantinib and atezolizumab due to AEs.
In light of these findings, “additional cohorts evaluating the combination in urothelial carcinoma have been initiated in cisplatin-ineligible and cisplatin-eligible disease without prior systemic therapy, as well as urothelial carcinoma previously treated with checkpoint-inhibitor therapy,” concluded Pal.
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