Bristol-Myers Squibb’s company announced that the European Commission has approved Opdivo (nivolumab) monotherapy for an additional indication in advanced renal cell carcinoma (RCC) after prior therapy in adults. Opdivo is the first and only PD-1 immune checkpoint inhibitor approved in Europe to demonstrate an overall survival (OS) benefit versus a standard of care in this patient population. This approval allows for the expanded marketing of Opdivo in previously treated advanced RCC in all 28 Member States of the European Union.
This approval is based on the results of the Phase 3 study CheckMate -025, which were published in The New England Journal of Medicine. In CheckMate -025, Opdivo was evaluated in patients with advanced clear-cell RCC who received prior anti-angiogenic therapy compared to everolimus. Patients treated with Opdivo achieved a median OS of 25 months versus 19.6 months for everolimus (HR=0.73 [98.5% CI: 0.57-0.93; p=0.0018]), representing a greater than five month improvement over a current standard of care. CheckMate -025 also evaluated patients’ quality of life (QoL) and found that patients treated with Opdivo had improved survival and QoL compared to everolimus throughout the duration of treatment.
CheckMate -025 is an open-label, randomized Phase 3 study, which evaluated Opdivo versus everolimus in patients with advanced clear-cell renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy, with overall survival (OS) as the primary endpoint. Objective response rate (ORR) was evaluated as a secondary endpoint. In the study, patients were randomized to receive Opdivo (3 mg/kg administered intravenously every two weeks) compared to everolimus (10 mg administered orally daily). The prespecified interim analysis was conducted when 398 events were observed (70% of the planned number of events for final analysis).
Results from CheckMate -025 showed that patients treated with Opdivo achieved a more than five month improvement in OS, with median OS of 25 months for Opdivo and 19.6 months for everolimus (HR=0.73 [98.5% CI: 0.57-0.93; p=0.0018]). An OS benefit was seen regardless of PD-L1 expression. In addition to improving OS, Opdivo demonstrated a superior ORR compared to everolimus (25.1% [95% CI: 21-29.6] vs. 5.4% [95% CI: 3.4-8.0]). Forty-nine (47.6%) Opdivo responders had ongoing responses of up to 27.6 months.
The safety profile of Opdivo in CheckMate -025 was consistent with prior studies. Serious adverse events occurred in 47% of patients receiving Opdivo. The most frequent serious adverse reactions reported in at least 2% of patients receiving Opdivo were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In the study, the most common adverse reactions (≥20%) reported in patients receiving Opdivo versus everolimus were asthenic conditions (56% vs. 57%), cough (34% vs. 38%), nausea (28% vs. 29%), rash (28% vs. 36%), dyspnea (27% vs. 31%), diarrhea (25% vs. 32%), constipation (23% vs. 18%), decreased appetite (23% vs. 30%), back pain (21% vs. 16%), and arthralgia (20% vs. 14%).
