Dr. McGregor on Cabozantinib Plus Atezolizumab in Non–Clear Cell RCC

Bradley McGregor, MD, a senior physician and the clinical director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, and an instructor in medicine at Harvard Medical, discusses the investigation of cabozantinib (Cabometyx) plus atezolizumab (Tecentriq) in patients with non–clear cell renal cell carcinoma (RCC).

The phase 1/2 COSMIC-021 trial (NCT03170960) evaluated the combination across multiple cohorts of patients with genitourinary cancers, including those with non–clear cell RCC in cohort 10. Findings presented at the 2023 Genitourinary Cancers Symposium showed that at a median follow-up of 37.2 months, cabozantinib plus atezolizumab elicited a disease control rate of 94% (95% CI, 79.2%-99.2%), including an objective response rate (ORR) of 31% (95% CI, 16.1%-50.0%).

Additionally, the median overall survival (OS) was not yet reached, and the 12-, 24-, and 36-month OS rates were 84% (95% CI, 66%-93%), 70% (95% CI, 50%-83%), and 54% (95% CI, 34%-71%), respectively. The median progression-free survival (PFS) was 9.3 months (95% CI, 5.5-12.3), and the 12- and 24-month PFS rates were 34% (95% CI, 18%-50%) and 6% (95% CI, 1%-24%), respectively.

Previously reported findings from the COSMIC-021 trial, which focused on median follow-up data of approximately 1 year, McGregor says. Cohort 10 features patients variant histology RCC, including papillary or chromophobe, McGregor adds. Patients were given oral cabozantinib at 40 mg per day plus intravenous atezolizumab at 1200 mg once every 3 weeks.

Moreover, patients remained on the treatment until unacceptable toxicity or clinical progression; however, patients who experienced radiographic progression but were still deriving clinical benefit from the combination could remain on therapy, McGregor continues,

At longer-term follow-up, the ORR was comparable with previously reported data. Additionally, there were no new toxicity signals, and 5 patients remained on therapy as of data cutoff, McGregor says. Notably, some of these patients had radiographic progression, and then developed radiographic regression again, highlighting that some patients could experience a durable benefit, McGregor concludes.