Nivolumab showed antitumor activity in patients with metastatic renal cell carcinoma

Nivolumab showed antitumor activity with a manageable safety profile in previously treated patients with clear-cell metastatic renal cell carcinoma, according to results of a randomized phase 2 trial.

“The results demonstrated longstanding objective responses and a favorable overall survival outcome compared to historical control for nivolumab in metastatic renal cell carcinoma patients who had previously progressed on VEGF-targeted drugs, supporting further study in a phase 3 trial,” researcher Robert J. Motzer, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, told HemOnc Today.

Nivolumab (Opdivo, Bristol-Myers Squibb) – a fully human immunoglobulin G4 programmed death (PD)-1 checkpoint inhibitor antibody — can restore T-cell activity in vitro by blocking the interaction between PD-1 and PD-L1 and PD-L2, according to background information in the study. This action potentially produces antitumor activity.

“An understanding of the mechanisms involved in the pathogenesis of renal cell carcinoma led to development of treatment options that inhibit VEGF-mediated signaling or the mammalian target of rapamycin pathway,” Motzer and colleagues wrote. “Although these treatment options have demonstrated PFS benefit, most patients with metastatic renal cell carcinoma (mRCC) eventually experience progression, underscoring the need for treatment options with novel mechanisms of action that could potentially result in improved efficacy and a survival advantage.”

Investigators conducted a masked, randomized, multicenter trial in which they administered three different doses of nivolumab to patients with mRCC. The dose-response relationship as measured by PFS served as the primary endpoint. Secondary endpoints included objective response rate, OS and safety.

Eligible patients had a histologic confirmation of RCC with clear-cell component and RECIST-defined measurable disease.

The analysis included 168 patients at 39 participating sites who were assigned at a ratio of 1:1:1 to one of three nivolumab treatment groups: 0.3 mg/kg, 2 mg/kg or 10 mg/kg. Treatment was administered intravenously on the first day of a 3-week treatment cycle.

Nivolumab demonstrated antitumor activity in all three study arms, although no dose-response relationship was observed. Median PFS was 2.7 months in the 0.3-mg/kg cohort, 4 months in the 2-mg/kg cohort and 4.2 months in the 10-mg/kg cohort (P=.9). ORRs were 20% in the 0.3-mg/kg cohort, 22% in the 2-mg/kg cohort and 20% in the 10-mg/kg cohort.

Researchers reported median OS of 18.2 months (80% CI, 16.2-24) in the 0.3-mg/kg group, 25.5 months (80% CI, 19.8-28.8) in the 2-mg/kg cohort and 24.7 months (80% CI, 15.3-26) in the 10-mg/kg cohort.

The most common adverse event reported was fatigue, observed in 24% of patients assigned the 0.3-mg/kg dose, 22% of patients assigned the 2-mg/kg dose and 35% of patients assigned the 10-mg/kg dose.

“Our results add to a growing body of evidence supporting the efficacy of nivolumab immunotherapy in mRCC.” Motzer and colleagues wrote. “There are a number of ongoing studies that will further elucidate this evidence, including a phase 3 trial comparing nivolumab vs. everolimus using an OS primary endpoint in patients with mRCC pretreated with antiangiogenic therapy.”

Disclosure: The researchers report research funding, honoraria or other remuneration from; employment relationships with; stock or other ownership in; and consultant/advisory or speakers’ bureau roles with Amgen, Bayer/Onyx, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Merck, Pfizer, Roche and other pharmaceutical companies.

Robert J. Motzer, MD, can be reached at Memorial Sloan-Kettering Cancer Center, Memorial Hospital, 1275 York Ave., New York, NY 10021; e-mail: motzerr@mskcc.org.