Nivolumab prior to surgery appears safe, effective in metastatic renal cell carcinoma

CHICAGO — Nivolumab plus or minus bevacizumab or ipilimumab prior to surgery appeared safe and demonstrated promising clinical activities in patients with metastatic renal cell carcinoma, according to study results presented at ASCO Annual Meeting.

Jianjun Gao, MD, PhD, an assistant professor in the department of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center, and colleagues conducted an open-label, randomized, pre-surgical trial of adults with metastatic renal cell carcinoma to determine if the combination of nivolumab (Opdivo, Bristol-Myers Squibb) and bevacizumab (Avastin, Genentech) or nivolumab and ipilimumab (Yervoy, Bristol-Myers Squibb) would safely lead to measurable immunologic changes and improved clinical activity.

Patients were excluded from the study if they had received prior immune checkpoint inhibitor therapy, as well as anti-VEGF therapy.

Patients were randomized to receive three doses of nivolumab (n = 29; median age, 57 years; 76% male) 3 mg/kg every 2 weeks, nivolumab and three doses of bevacizumab (n = 40; median age, 60 years; 70% male) 10 mg/kg, or nivolumab and two doses of ipilimumab (n = 30; median age, 61 years; 93% male) 1 mg/kg followed by either cytoreductive nephrectomy or metastasectomy and up to 2 years of nivolumab maintenance therapy.

Safety and tolerability served as the primary endpoints.

The secondary endpoints included immunological changes in pre- and post-treatment tumor and blood samples.

Researchers assessed best overall responses including partial and complete response at a minimum of 12 weeks after therapy.

Best overall response in the nivolumab arm was 54% including 4% complete response; 48% (3% complete response) in the nivolumab and bevacizumab arm; 41% (3% complete response) in the nivolumab and ipilimumab arm.

Best overall response in 42 evaluable patients who proceeded onto therapy was 79% in the nivolumab arm (n = 14), 93% in the nivolumab and bevacizumab (n = 15) and 69% in the nivolumab and ipilimumab (n = 13).

Grade 3 or higher adverse events occurred in 24% of patients who received nivolumab, 31% of patients who received nivolumab and bevacizumab, and 30% of patients who received nivolumab and ipilimumab.

The researchers acknowledged that more research is needed.

“Combination therapy [plus or minus] bevacizumab or ipilimumab followed by cytoreductive surgery deserves to be tested in a larger phase 3 trial,” the researchers wrote. “Immune and molecular correlative studies may allow to identify novel biomarkers that can be used for correlation with clinical outcomes in patients with metastatic renal cell carcinoma.” – by Ryan McDonald

Reference:

Gao J, et al. Abstract 4520. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

Disclosures: Gao reports travel, accommodation and expense support from AstraZeneca.