The European Commission has approved a combination of Opdivo (nivolumab) and low-dose Yervoy (ipilimumab) for the initial treatment of advanced renal cell carcinoma patients with intermediate and poor risk, making it the first immunotherapy combination approved in Europe for this cancer.
The decision was based on results from the Phase 3 CheckMate-214 trial (NCT02231749), in which the combination significantly extended survival, delayed disease progression or death, and increased responses, compared with the standard of care, Sutent (sunitinib).
“We are extremely pleased that the European Commission has approved Opdivo plus low-dose Yervoy based on the significant survival benefit demonstrated in the CheckMate -214 trial,” Chris Boerner, PhD, chief commercial officer of Bristol-Myers Squibb, said in a press release. “Today’s approval helps further our goal of transforming the way cancer is treated and increasing quality, long-term survival for patients.”
Sutent, an inhibitor of the VEGF receptor, is the standard first-line treatment for patients with advanced renal cell carcinoma, reducing tumors in approximately 25% of patients and keeping them alive and without signs of disease progression for a median of 9.5 months.
Results from a Phase 1 trial (NCT01472081), however, suggested that a combination of Opdivo and low-dose Yervoy may be better for these patients. In the trial, 40% of patients responded to the combination, and up to 70% lived two years or longer.
To confirm the findings, researchers conducted a Phase 3 trial comparing the safety and efficacy of Opdivo plus low-dose Yervoy versus Sutent in advanced renal cell carcinoma patients who had not received any prior treatments.
CheckMate-214 included 1,082 patients — 423 with intermediate risk and 416 with poor risk — randomly assigned the immunotherapy combination — Opdivo plus Yervoy given as an infusion every three weeks for four doses, and Opdivo every two weeks thereafter — or once-daily, oral Sutent – in a four weeks on, two weeks off regimen.
The trial’s main objective was to determine if the combination was better than Sutent at improving overall survival, extending the time patients lived without disease worsening, and reducing tumor burden in patients with intermediate to poor risk.
After a median follow-up of 25.2 months, more patients had responded to the combination than to Sutent — 42% versus 27% — and more patients had seen their cancer disappear — 9% versus 1%. At the time of the analysis, more than half of patients were still responding to the combination, while the median duration of response to Sutent was 18.2 months.
Three in four patients receiving the combination lived past the 18-month mark, compared with 60% of those receiving Sutent. In addition, patients on the combination lived 11.6 months without their disease progressing, compared with 8.4 months for Sutent. Overall, this represented a 37% reduction in the risk of death and an 18% reduction in the risk of disease progression or death.
In addition to the survival benefits, the Opdivo-Yervoy combination led to fewer severe or life-threatening adverse events than Sutent — 46% versus 63%. However, more patients in the combination group discontinued due to treatment-related adverse events — 22% versus 12%.
“Currently, less than 50% of patients with metastatic renal cell carcinoma survive beyond two years, and there is almost no complete remission observed, which underscores the need for new treatments for this disease,” said Bernard Escudier, MD, ex-chairman of the genitourinary oncology committee at the Institut Gustave Roussy. “Today’s approval offers patients in the European Union a first-line treatment option that has demonstrated a complete response rate of almost 10% and a significant improvement in overall survival with fewer Grade 3 and 4 adverse reactions compared to sunitinib.”