In the phase Ib COSMIC-021 trial reported in the Journal of Clinical Oncology, Sumanta K. Pal, MD, FASCO, and colleagues found that the combination of cabozantinib and atezolizumab produced durable responses in patients with advanced renal cell carcinoma (RCC).
Sumanta K. Pal, MD, FASCO
Study Details
One hundred and two patients from sites in the United States, France, and Spain were enrolled into the open-label trial between September 2017 and November 2019. Patients with clear cell RCC received cabozantinib at 40 mg (n = 34) or 60 mg once daily (n = 36) plus atezolizumab at 1,200 mg every 3 weeks. Patients with non–clear cell RCC (RCC) received cabozantinib at 40 mg once daily plus atezolizumab (n = 32). Treatment was continued until disease progression or unacceptable toxicity. No patients with clear cell RCC had received prior systemic therapy except for two (adjuvant sunitinib and pazopanib). A total of seven patients in the non–clear cell RCC cohort had received prior systemic therapy with a VEGFR inhibitor.
Responses
Median follow-up was 25.8, 15.3, and 13.3 months for the 40-mg clear cell RCC, 60-mg clear cell RCC, and non–clear cell RCC groups, respectively.
Objective response was observed in 18 patients (53%, 80% confidence interval [CI] = 41%–65%) in the 40-mg clear cell RCC group (complete response in 1, 4%) and in 21 patients (58%, 80% CI = 46%–70%) in the 60-mg clear cell RCC group (complete response in 4, 11%). Median durations of response were not reached (95% CI = 12.4 months–not estimable) and 15.4 months (95% CI = 8.1 months–not estimable). Disease control rates were 94% and 92%. Median progression-free survival was 19.5 months (95% CI = 11.0 months–not estimable) and 15.1 months (95% CI = 8.2–22.3 months), with 1-year rates of 67% and 58%.
Among patients with non–clear cell RCC, objective response (all partial responses) was observed in 10 patients (31%, 80% CI = 20%–44%), including response in 7 (47%) of 15 with papillary RCC. Median duration of response was 8.3 months (95% CI = 2.4 months–not estimable). The disease control rate was 94%. Median progression-free survival was 9.5 months (95% CI = 6.4–18.3 months), with a 1-year rate of 39%.
KEY POINTS
- Objective response rates in the clear cell RCC cohorts were 53% and 58% with cabozantinib at 40 and 60 mg plus atezolizumab, and 31% in the non–clear¬ cell RCC cohort.
- Disease control rates were > 90% in all three groups.
Adverse Events
Grade 3 or 4 treatment-related adverse events occurred in 71% of the 40-mg clear cell RCC group (most commonly hypertension [24%] and hypophosphatemia [15%]), 67% of the 60-mg clear cell RCC group (most commonly diarrhea [19%], hypertension [14%], and increased alanine transaminase [14%]), and 38% of the non–clear cell RCC group (most commonly hypophosphatemia [13%]). Treatment-related adverse events leading to discontinuation of either or both drugs occurred in 24% and 15%, 19% and 6%, and 16% and 3% of the three groups, respectively. No treatment-related deaths were reported.
The investigators concluded, “The novel combination of cabozantinib plus atezolizumab demonstrated encouraging clinical activity and acceptable tolerability in patients with advanced clear cell and non–clear cell RCC. Disease control was observed across dose levels and histologic subtypes.”
Dr. Pal, of the Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Exelixis Inc. For full disclosures of the study authors, visit ascopubs.org.
