Bristol-Myers Squibb 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.

Emmanuel Blin, senior vice president, Head of Commercialization, Policy and Operations, Bristol-Myers Squibb, commented, “Today’s approval is reflective of our commitment to bring Opdivo and the potential for long-term survival to broad patient populations, including previously treated advanced renal cell carcinoma. Opdivo is the only PD-1 inhibitor approved in Europe to demonstrate a significant survival advantage in this patient population. At Bristol-Myers Squibb, we are driven to work with speed to deliver new treatment options to help more patients, and in less than a year, we have expanded the approval of Opdivo in Europe to include three distinct types of advanced cancer.”

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 per cent 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.

Dr. Bernard Escudier, Chair of the Genitourinary Oncology Committee, Institut Gustave Roussy in Villejuif, France, commented, “For the first time, previously treated advanced renal cell carcinoma patients in Europe will now have access to an Immuno-Oncology agent that has demonstrated a significant overall survival benefit along with a favorable safety profile compared to everolimus. In addition to the clinical efficacy results, patients treated with Opdivo experienced an improvement in their health-related quality of life and had significantly lower symptom burden throughout treatment compared to patients receiving everolimus. Combined, these data support the use of Opdivo in clinical practice and represent important progress toward establishing a new standard of care in Europe.”

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 per cent 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 per cent 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 per cent [95 per cent CI: 21-29.6] vs. 5.4 per cent [95 per cent CI: 3.4-8.0]). Forty-nine (47.6 per cent) Opdivo responders had ongoing responses of up to 27.6 months.

In addition to the OS benefit observed with Opdivo, patients treated with the drug also experienced an improvement over time in disease related symptoms and non-disease specific quality of life compared to patients receiving everolimus. Patients were assessed using validated and reliable scales in the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) and the EuroQoL EQ-5D. Results showed that as early as week 20, patients receiving Opdivo had a significant improvement in disease related symptoms, while patients receiving everolimus showed a significant deterioration by week 4.

The safety profile of Opdivo in CheckMate -025 was consistent with prior studies. Serious adverse events occurred in 47 per cent of patients receiving Opdivo. The most frequent serious adverse reactions reported in at least 2 per cent of patients receiving Opdivo were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In the study, the most common adverse reactions (=20 per cent) reported in patients receiving Opdivo versus everolimus were asthenic conditions (56 per cent vs. 57 per cent), cough (34 per cent vs. 38 per cent), nausea (28 per cent vs. 29 per cent), rash (28 per cent vs. 36 per cent), dyspnea (27 per cent vs. 31 per cent), diarrhea (25 per cent vs. 32 per cent), constipation (23 per cent vs. 18 per cent), decreased appetite (23 per cent vs. 30 per cent), back pain (21 per cent vs. 16 per cent), and arthralgia (20 per cent vs. 14 per cent).

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, accounting for more than 100,000 deaths worldwide each year. Clear-cell RCC is the most prevalent type of RCC and constitutes 80 per cent to 90 per cent of all cases. RCC is approximately twice as common in men as in women, with the highest rates of the disease in North America and Europe. Globally, the five-year survival rate for those diagnosed with metastatic, or advanced kidney cancer, is 12.1 per cent.