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Atezolizumab plus bevacizumab safe, active in non-clear cell, sarcomatoid kidney cancer
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SAN FRANCISCO — The combination of atezolizumab and bevacizumab demonstrated antitumor activity and appeared safe in patients with non-clear cell renal cell carcinoma, according to results of a phase 2 study presented at Genitourinary Cancers Symposium.
This treatment showed similar activity with manageable toxicity in patients with clear cell renal cell carcinoma with sarcomatoid differentiation.
“Non-clear cell renal cell carcinoma comprises 20% of all renal cell carcinoma histologies, and sarcomatoid differentiation can coexist with any renal cell carcinoma subtype,” Rana R. McKay, MD, assistant professor of medicine and medical oncologist at University of California, San Diego, said during the presentation. “These entities comprise a heterogenous group of diseases with different tumor biologies and molecular characterizations, and compared to clear cell renal cell carcinoma, they have historically had inferior survival.”
In the multicenter phase 2, open-label, single-arm study, McKay and colleagues evaluated 42 patients (median age, 62 years; interquartile range [IQR], 53-69) with non-clear cell renal cell carcinoma (20% papillary; 16.7% chromophobe; 15% unclassified; 8.3% collecting duct; 8.3% translocation; 1.7% medullary) and 18 patients with clear cell renal cell carcinoma with more than 20% sarcomatoid differentiation.
Participants had an ECOG performance status of 0 to 2 and 21 received prior systemic therapy, including 20 patients with non-clear cell renal cell carcinoma. The trial did not include patients who previously received PD-1 or PD-L1 therapy.
After a required baseline biopsy, patients received 120 mg atezolizumab (Tecentriq, Genentech) and 15 mg IV bevacizumab (Avastin, Genentech) every 3 weeks. Treatment continued until disease progression, unacceptable adverse events or withdrawal from the study.
Objective response rate based on RECIST 1.1 criteria served as the study’s primary endpoint. Secondary endpoints included duration of response, PFS, OS, immune-related objective response and toxicity.
Median follow-up was 9.7 months. The final analysis included 56 patients.
Results showed an ORR of 34% in the overall cohort, including 31% of treatment-naive patients and 40% of previously treated patients. Patients with non-clear cell renal cell carcinoma had an ORR of 26%, and those with clear cell renal cell carcinoma had an ORR of 53%.
Nearly one-quarter of the cohort (23%) had stable disease at more than 24 weeks, and 57% demonstrated clinical benefit, with a median duration of response of 24 weeks.
Researchers observed median PFS of 8.4 months (95% CI, 6.9-16.5) and median OS of 21.2 months (95% CI, 16.8-not estimable).
Nineteen patients (37%) experienced grade 3 adverse events, including diarrhea, aspartate aminotransferase increase, fatigue and fever. Patients experienced no grade 4 to grade 5 toxicities; however, five (8%) discontinued treatment due to toxicities.
“Atezolizumab and bevacizumab demonstrated antitumor activity in patients with non-clear cell renal cell carcinoma and patients with clear cell renal cell carcinoma with sarcomatoid differentiation,” McKay said. “Treatment was tolerable with manageable toxicities, and correlative studies are currently underway exploring both biomarkers of response and resistance. Obviously, future studies are warranted to explore immunotherapy and novel combinations in this very unique patient population.” – by Jennifer Byrne
Reference:
McKay RR, et al. Abstract 244057. Presented at: Genitourinary Cancers Symposium; Feb. 14-16, 2019; San Francisco.
Disclosures: McKay reports a consultant/advisory role with Bristol-Myers Squibb/Pfizer, Exelixis, Janssen, Novartis and Tempus, and institutional research funding from Bayer and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.