An immune checkpoint inhibitor provides “a real opportunity to change clinical practice” for patients with metastatic renal cell carcinoma, a study author says.
Nivolumab, an immunotherapy drug, has shown a significant survival benefit in patients with metastatic renal cell carcinoma and has been granted breakthrough therapy designation from the FDA for the potential indication of metastatic RCC.
Researchers say the study marks the first time an immune checkpoint inhibitor has been proven to increase survival among patients with advanced RCC.
For the CheckMate-025 study, researchers at the University of Texas MD Anderson Cancer Center, Dallas, compared nivolumab, an FDA-approved immunotherapy agent, with everolimus (Afinitor). Nivolumab, an immune checkpoint inhibitor marketed as Opdivo, is currently used to treat metastatic melanoma and advanced non-small cell lung cancer.
“Immunotherapy has long been believed to have the potential to make an impact in kidney cancer, but until now we had not been able to demonstrate such a significant survival benefit. We have a real opportunity to change clinical practice for patients when other therapies have failed,” said principal investigator Padmanee Sharma, MD, PhD, in a press release from MD Anderson.
In the randomized phase III clinical trial, which was published online in the New England Journal of Medicine (Sept. 25, 2015) and presented at the European Cancer Congress in Vienna, Austria, patients whose disease progressed on antiangiogenic therapies were treated with either nivolumab or everolimus. Median overall survival was 5.4 months longer with nivolumab (25 months) compared with everolimus (19.6 months).
The study included 821 patients with advanced RCC across 151 sites in 24 countries in North America, Europe, Australia, South America, and Asia. All had previously been treated with one or two antiangiogenic therapies. The median duration of treatment was 5.5 months with nivolumab and 3.7 months with everolimus.
In addition to demonstrating increased overall survival, the authors showed a higher objective response rate with nivolumab. Of the 821 patients enrolled, 25% responded to nivolumab versus 5% of those treated with everolimus. Among these patients, partial responses were observed in 24% of those treated with nivolumab and 5% of patients treated with everolimus; complete responses were observed in 1% (four patients) treated with nivolumab and fewer than 1% (two patients) treated with everolimus.
Further, among patients who showed a response, the impact was “durable,” according to Dr. Sharma. While median progression-free survival appeared similar between nivolumab and everolimus (4.6 months and 4.4 months, respectively), when the authors explored a delayed progression-free survival benefit at 6 months, they reported 15.6 months with nivolumab and 11.7 months with everolimus. This ongoing response was observed among 44% of those treated with nivolumab and 36% of those treated with everolimus. More than 12 months later, 31% and 27% of patients treated with nivolumab and everolimus, respectively, continued to show a response.
Finally, the investigators observed fewer treatment-related adverse events, including fatigue and nausea, and improved quality of life with nivolumab.
These results led the trial to be halted early in July 2015 when an assessment conducted by the independent Data Monitoring Committee concluded that the study met its primary endpoint, demonstrating superior overall survival in patients receiving nivolumab.
Based on the CheckMate-025 findings, the FDA recently granted breakthrough therapy designation to nivolumab for the potential indication of metastatic RCC.
Bristol-Myers Squibb provided support for the study. Dr. Sharma is a consultant for Amgen, Bristol-Myers Squibb, GlaxoSmithKline, and AstraZeneca/MedImmune. She is a consultant and founder of Jounce Therapeutics. For full disclosures of all authors, click here.
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