ASCO GU 2019: Results of a Phase II Study of Atezolizumab and Bevacizumab in Non-clear Cell Renal Cell Carcinoma and Clear Cell Renal Cell Carcinoma with Sarcomatoid Differentiation
NccRCC and sccRCC comprise 20% of all RCC cases, and sarcomatoid differentiation can coexist with any RCC subtype. They comprise a heterogeneous group of diseases with differing tumor biology and molecular characterization and have inferior survival when compared to clear cell RCC even with targeted therapy. NccRCC and sccRCC have historically been underrepresented in clinical trials. The combination of atezolizumab and bevacizumab has demonstrated safety and efficacy in ccRCC. In this multicenter, phase II, open-label, single arm trial the efficacy of atezolizumab and bevacizumab was evaluated in patients with nccRCC and sccRCC with >20% sarcomatoid differentiation.
Dr. McKay then summarized the study design of this phase II study. Eligible patients had an ECOG performance status of 0-2 and may have received prior therapy. Prior PD-1/PD-L1 therapy was not allowed. Patients underwent a mandatory baseline biopsy and subsequently received atezolizumab 120 mg and bevacizumab 15 mg/kg intravenously every 3 weeks. Patients remained on therapy until radiographic progression, unacceptable adverse events, or withdrawal. The primary endpoint was overall response rate (ORR) as determined by RECIST version 1.1.
Dr. McKay then highlighted the results of the study. 60 patients who had ≥1 response assessment were included in this analysis. 42 patients had nccRCC, and 18 patients had sccRCC. 21 patients received prior systemic therapy, 20 of whom had nccRCC. The ORR was 34% in the overall cohort, and it was higher in PD-L1 positive patients. 19 patients (37%) developed grade 3 treatment-related adverse events (AEs). There were no grade 4-5 AEs.
Dr. Mckay then concluded her presentation with a summary that therapy with atezolizumab and bevacizumab was safe and demonstrated anti-tumor activity in nccRCC and sccRCC. Responses appeared higher in PD-L1 positive patients. Treatment was tolerable with manageable toxicity, and correlative studies exploring biomarkers of response and resistance are underway. She stressed that there is a need for future studies to explore immunotherapy and novel combinations in this patient population.
Presented by: Rana R. McKay, MD, Medical Oncologist, Assistant Professor of Medicine, UC San Diego Health
Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Fox Chase Cancer Center, Philadelphia, PA at the Annual ASCO GU meeting 2019, San Francisco, CA, Twitter: @shekabhishek at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA