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Monoclonal Antibody Combination Under Study in Rare Metastatic Kidney Cancer

By: Celeste L. Dixon
Posted: Thursday, January 16, 2020

The prognosis of patients with either variant histology renal cell carcinoma or clear cell renal cell carcinoma with sarcomatoid differentiation tends to be worse than that of patients with conventional clear cell renal cell carcinoma, but they are historically excluded from many phase III studies. Bradley A. McGregor, MD, of Dana-Farber Cancer Institute, Boston, and colleagues created a multicenter phase II trial to evaluate, in that renal cell carcinoma patient subgroup, a combination treatment with previous evidence of increased antitumor immunity in the conventional clear cell renal cell carcinoma population. The combination—bevacizumab plus atezolizumab, monoclonal antibodies against VEGF-A and PD-L1, respectively—indeed showed clinical efficacy and was well tolerated, the researchers reported in the Journal of Clinical Oncology.

Eligible patients could have received previous systemic therapy, excluding bevacizumab or checkpoint inhibitors, but 65% were treatment-naive. In total, 60 patients with advanced disease received at least one dose of the combination (median cycles = 9.5). A total of 42 patients had variant histology renal cell carcinoma and 18 had clear cell renal cell carcinoma with at least 20% sarcomatoid differentiation.

“The overall response rate for the overall population was 33%...50% in patients with clear cell renal cell carcinoma with sarcomatoid differentiation and 26% in patients with variant histology renal cell carcinoma,” wrote Dr. McGregor and colleagues. The median progression-free survival was 8.3 months. Of the 36 patients for whom PD-L1 status was available, 42% had at least 1% expression on tumor cells. The overall response rates in PD-L1–positive (60%) and PD-L1–negative (19%) patients were significantly different (P = .01). No patients developed grade 4 or 5 treatment-related toxicities; eight patients developed grade 3 toxicities.

“The combination demonstrated responses across several subtypes of renal cell carcinoma, including collecting duct and medullary carcinoma, histologies that are often treated with cytotoxic chemotherapy,” the team pointed out. More trials should evaluate “immune checkpoint inhibitor combinations in this diverse patient population….”

Disclosure: For full disclosures of the study authors, visit ascopubs.org.



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