Study Supports Added Benefit of Nivolumab (Opdivo) in Renal Cell Carcinoma

Investigators find “major” benefit versus everolimus in poor-prognosis patients

Nivolumab (Opdivo, Bristol-Myers Squibb) is approved as a checkpoint inhibitor for the treatment of adults with advanced renal cell carcinoma (RCC) who have received prior antiangiogenic therapy. The German Institute for Quality and Efficiency in Health Care has investigated whether this monoclonal antibody offers advantages over a comparator therapy (everolimus or temsirolimus) in patients with RCC.

The findings indicated a “major” added benefit for nivolumab in RCC patients with a poor prognosis (i.e., a high Memorial Sloan Kettering Cancer Center [MSKCC] score) compared with everolimus, according to the investigators. In patients with a favorable or intermediate prognosis, the added benefit of nivolumab was judged to be “considerable.”

Specifically, in patients with a poor prognosis, the data indicated an added benefit for nivolumab in terms of overall survival (OS); in contrast, no indication of an added OS benefit was observed in patients with a favorable or intermediate MSKCC score.

Nivolumab also showed advantages over everolimus for two morbidity outcomes (symptoms and health status), as well as for several outcomes in the category of adverse effects (discontinuation due to adverse events, severe adverse events, and specific adverse events).

Overall, in patients with favorable or intermediate MSKCC scores, the data showed a “considerable” added benefit for nivolumab over everolimus, according to the investigators. In patients with a poor prognosis, the data indicated a “major” added benefit.

No added benefit was observed in patients who had received prior treatment with temsirolimus.

In the pivotal, open-label trial used to support the regulatory submission of nivolumab in the United States, patients with advanced RCC who had experienced disease progression during or after one or two prior antiangiogenic regimens were randomly assigned to receive either intravenous nivolumab (3 mg/kg every two weeks; n = 410) or oral everolimus (10 mg daily; n = 411). The patients’ median age was 62 years (range, 18 to 88 years), and most were male (75%) and white (88%). Patient distribution by MSKCC risk groups was 34% favorable, 47% intermediate, and 19% poor. The primary efficacy outcome was OS.

The trial demonstrated a statistically significant improvement in OS in the patients treated with nivolumab compared with those given everolimus. The median OS for nivolumab was 25.0 months compared with 19.6 months for everolimus (hazard ratio, 0.73; P = 0.0018). In addition, nivolumab had a confirmed objective response rate of 21.5% compared with 3.9% for everolimus.

Nivolumab is a human monoclonal antibody that blocks interactions between the programmed death-1 (PD-1) receptor and its ligands, PD-L1 and PD-L2. This activity, in turn, allows PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

Sources: EurekAlert; August 10, 2016; and Opdivo Prescribing Information; May 2016.