Results from CheckMate -025, a phase 3 study comparing Nivolumab ( Opdivo ) to Everolimus ( Afinitor ) in advanced renal cell carcinoma ( RCC ) after prior anti-angiogenic treatment, showed a significant overall survival ( OS ) benefit for Nivolumab.
In the trial, Nivolumab demonstrated a median overall survival benefit of 25 months compared to 19.6 months for Everolimus. Clinical benefit for Nivolumab was observed regardless of level of PD-L1 expression.
The safety profile shown in CheckMate -025 is consistent with previously reported trials with Nivolumab.
These data were presented at European Cancer Congress ( ECC2015 ).
Approximately 30% of patients with renal cell carcinoma, a common type of kidney cancer in adults, present with metastatic or advanced disease at diagnosis. Despite multiple available treatment approaches for advanced renal cell carcinoma, available second-line therapies are associated with limited overall survival, and significant toxicities and limitations in tolerability, with the majority of current treatment options providing modest progression-free survival benefit.
CheckMate -025 was stopped in July because an assessment conducted by the independent Data Monitoring Committee ( DMC ) concluded that the study met its primary endpoint, demonstrating superior overall survival in patients receiving Nivolumab compared to the control arm.
Opdivo was granted Breakthrough Therapy Designation for advanced renal cell carcinoma by the U.S. Food and Drug Administration ( FDA ) based on results from this trial and the clinical need for additional treatment approaches for renal cell carcinoma.
CheckMate -025 is a phase 3 randomized, open-label study of Nivolumab versus Everolimus in previously treated patients with advanced clear-cell renal cell carcinoma after prior anti-angiogenic treatment.
Patients were randomized to receive Nivolumab ( n=410 ) 3 mg/kg intravenously every two weeks or Everolimus ( n=411 ) 10 mg orally once daily.
The primary endpoint was overall survival ( OS ). Secondary endpoints included objective response rate ( ORR ), progression-free survival ( PFS ), overall survival by PD-L1 expression, and incidence of adverse events.
Results from CheckMate -025 mark the first and only phase 3 study to demonstrate a significant survival advantage in previously treated patients with advanced renal cell carcinoma versus standard of care.
Patients treated with Nivolumab in this study achieved a median overall survival of 25 months for Nivolumab and 19.6 months for Everolimus ( hazard ratio, HR=0.73; [ 98.5% CI, 0.57-0.93; p=0.0018 ] ), with comparable overall survival benefit seen across PD-L1 expression levels.
In addition to improving overall survival, Nivolumab demonstrated a superior ORR of 25% versus 5% for Everolimus ( p less than 0.0001 ), with one out of four patients experiencing a response. Seventeen percent of Nivolumab and 7% of Everolimus patients remain on treatment with a minimum follow-up of 14 months.
The safety profile of Nivolumab in CheckMate -025 was consistent with prior studies and favorable versus Everolimus. Fewer grade 3-4 treatment-related adverse effects occurred with Nivolumab ( 19% ) compared to Everolimus ( 37% ).
Any grade treatment-related adverse reactions occurred in 79% of patients treated with Nivolumab and 88% of patients treated with Everolimus.
The most frequent treatment-related adverse effects were fatigue ( 33% ), pruritus ( 14% ), and nausea ( 14% ) in the Nivolumab arm and fatigue ( 34% ) and stomatitis ( 30% ) in the Everolimus arm.
Renal cell carcinoma 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 renal cell carcinoma and constitutes 80% to 90% of all cases.
Renal cell carcinoma is approximately twice as common in men as it is in women, with the highest rates of the disease found in North America and Europe.
Globally, the five-year survival rate for those diagnosed with advanced kidney cancer is 12.1%.
Nivolumab is a programmed death-1 ( PD-1 ) immune checkpoint inhibitor. ( Xagena )
Source: BMS, 2015