Nivolumab Safe, Effective in mRCC

May 6, 2015

Treatment with the PD-1 inhibitor nivolumab was active and tolerable across three doses for patients with metastatic renal cell carcinoma.

Robert J. Motzer, MD

Treatment with the PD-1 inhibitor nivolumab (Opdivo) was active and tolerable across three doses for patients with metastatic renal cell carcinoma (mRCC), according to results from a phase II study published in theJournal of Clinical Oncology.

In the study, 168 patients with clear-cell mRCC received intravenous nivolumab at 0.3 mg/kg (n = 60), 2 mg/kg (n = 54), or 10 mg/kg (54) once every 3 weeks. Those enrolled in the study had received prior therapy with a VEGF-targeted therapy. The primary outcome measure was progression-free survival (PFS), with overall survival (OS) and objective response rates (ORR) as secondary outcome measures.

"Seventy percent of patients had received more than one prior systemic regimen, including 40% who had received two or three prior antiangiogenic drugs and approximately one third who had received prior everolimus," the authors noted.

In the two larger dose arms, the median PFS was 4.0 and 4.3 months and the median OS was 25.5 and 24.7 months, in the 2 mg/kg and 10 mg/kg arms, respectively. Median survival outcomes were lower in the 0.3 mg/kg arm, with a median PFS of 2.7 months and a median OS of 18.2 months. The ORR was similar at 20%, 22%, and 20% in the 0.3-, 2-, and 10-mg/kg arms, respectively.

"ORR was similar by treatment arm, ranging from 20% to 22% and including patients with ongoing, durable objective responses," the authors wrote. "At data cutoff, 40% of the 35 objective responders were still responding ≥24 months from start of nivolumab therapy."

PD-L1 Data Unclear

PD-L1 expression status was assessed, with a median PFS of 4.9 months in the PD-L1 ≥5% subgroup (positive) versus 2.9 months in the PD-L1 <5% subgroup (negative). The ORR was 31% in the PD-L1-positive group and 18% in the PD-L1-negative arm.

"Our data show that although response to treatment was higher in patients with greater PD-L1 expression (≥ 5%), those with lower PD-L1 expression (< 5%) also had meaningful responses," Motzer et al, explained. "These PD-L1 outcome data were assessed as an exploratory endpoint but are consistent with earlier published observations."

Adverse Events Mild

A majority of the patients enrolled in the study experienced an adverse event of any grade (73%), with 11% experiencing a grade 3/4 event. All-grade adverse events were similar across doses, at 75%, 67%, and 78% in the 0.3-, 2-, and 10-mg/kg groups, respectively. Grade 3/4 pneumonitis was not reported in the study.

Systemic corticosteroids were required for the managed of adverse events in more patients treated with the 10-mg/kg dose (33%) compared with the 0.3 (15%) and 2 mg/kg doses (19%).

"The frequency of treatment-related adverse events were similar across groups, and treatment-related adverse events were primarily low grade in severity," the authors wrote. "Cases of drug-related pneumonitis associated with fatal outcome were observed in the phase I trial in other tumor types, but no high-grade pneumonitis was observed in our trial."

Ongoing Study Commenced

"Findings from our dose-ranging study, coupled with analyses of safety and efficacy across tumor types from a large phase I study, support the selection of nivolumab 3 mg/kg intravenously every 2 weeks as the monotherapy dosing regimen for further study," Motzer et al, wrote.

A phase III trial is currently comparing treatment with nivolumab and everolimus using an OS primary endpoint in patients with mRCC who have been pretreated with antiangiogenic therapy (NCT01668784). Additionally, a phase III study is examining the combination of nivolumab and ipilimumab in comparison with single-agent sunitinib in previously untreated mRCC. The endpoint of this study is OS (NCT02231749).

Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial.J Clin Oncol. 2015;33(13):1430-1437.