Nivolumab May Improve Survival in Patients With Advanced RCC

For the first time, researchers have found that a checkpoint inhibitor may result in a survival advantage in advanced renal cell carcinoma (RCC), according to new data from an open-label, randomized, phase III study. 

The trial, which was evaluating nivolumab (Opdivo) compared to everolimus (Afinitor) in previously treated patients with advanced or metastatic RCC, was stopped early because it demonstrated superiority. An assessment conducted by the independent Data Monitoring Committee (DMC) concluded that the study met its endpoint, demonstrating superior overall survival (OS) in patients receiving nivolumab compared to the control arm.

“The results of CheckMate -025 mark the first time an immuno-oncology agent has demonstrated a survival advantage in advanced renal cell carcinoma, a patient group that currently has limited treatment options,” said Michael Giordano, MD, who is senior vice president, Head of Development in Oncology at Bristol-Myers Squibb.¹

Dr. Giordano said the company will complete a full evaluation of the final CheckMate -025 data and will work with investigators on the future presentation and publication of the results. 

CheckMate -025 is a phase III, open-label, randomized study of nivolumab versus everolimus in previously treated patients with advanced or metastatic clear cell RCC. The trial randomized 821 patients to receive either nivolumab 3 mg/kg intravenously every 2 weeks, or everolimus 10 mg tablets by mouth daily until documented disease progression or unacceptable toxicity. The primary endpoint was overall survival. Secondary endpoints include objective response rate and progression-free survival (PFS).

Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor, and is approved for patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. It is also approved for patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation-positive, a BRAF inhibitor.

Severe pneumonitis or interstitial lung disease, including fatal cases, have occurred with this agent. Across the clinical trial experience in 691 patients with solid tumors, fatal immune-mediated pneumonitis occurred in 0.7% (5/691) of patients receiving nivolumab.  Pneumonitis, including interstitial lung disease, has occurred, as well as diarrhea or colitis, in nivolumab-treated patients.  Other adverse events associated with this agent include increased incidence of liver enzymes, an increased incidence of elevated creatinine levels, and grade 1 or 2 hypothyroidism.

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% to 90% 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 5-year survival rate for those diagnosed with metastatic or advanced kidney cancer is 12.1%.

References:

• Bristol-Myers Squibb Press Release. (2015). CheckMate -025, a Pivotal Phase III Opdivo (nivolumab) Renal Cell Cancer Trial, Stopped Early.