FDA Approves Nivolumab for Renal Cell Carcinoma

Nick Mulcahy


November 23, 2015

The US Food and Drug Administration (FDA) today approved the immunotherapy nivolumab (Opdivo, Bristol-Myers Squibb) to treat patients with metastatic renal cell carcinoma whose disease progressed on an antiangiogenic therapy.

"[Opdivo] is one of few therapies that have demonstrated the ability to extend patients' survival in treating this disease," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research in a press statement.

Temsirolimus (Torisel, Pfizer), which was approved in 2007, is the only other FDA-approved therapy that has demonstrated an overall survival benefit in the treatment of advanced renal cell carcinoma compared with standard therapy.

However, nivolumab is the first treatment to show a survival benefit as second-line therapy.

There is an abundance of other approved targeted therapies for advanced renal cell carcinoma but these drugs have only been shown to improve progression-free survival.

"Opdivo provides an important therapy option for patients with renal cell carcinoma," Dr Pazdur said.

Nivolumab is a monoclonal antibody that neutralizes the programmed death 1 (PD-1) protein, an element of tumors that enables them to evade their nemesis, the immune system. The drug is also approved for use in advanced melanoma and advanced non-small cell lung cancer (both squamous and non-squamous)

In an open-label, phase 3 study of 821 patients with advanced renal cell carcinoma who stopped responding to antiangiogenic therapies, patients were randomly assigned to receive nivolumab or everolimus (Afinitor, Novartis), a standard therapy in this setting.

The median overall survival was 25 months with nivolumab vs 19.6 months with everolimus (hazard ratio, 0.73; P = .002).

In addition, more patients responded to the immunotherapy ― the objective response rate was 21.5% for nivolumab versus 3.9% for everolimus. And they responded longer: the median duration of response was 23 months for patients on nivolumab versus 13.7 months for those on everolimus.

Results from this trial, known as CheckMate 025, were first presented in September at the 2015 European Cancer Congress and simultaneously published in the New England Journal of Medicine(NEJM), as reported by Medscape Medical News.

"Nivolumab has set a new benchmark," said meeting discussant Cora Sternberg, MD, at that time; she is from the San Camillo-Forlanini Hospital, in Rome, Italy.

Nivolumab is the new standard of care in second-line therapy for advanced renal cell carcinoma, said other experts in an NEJM editorial.

"Given the overall survival advantage it confers and its relatively good side-effect profile, nivolumab is the choice for patients who have disease progression while they are receiving [vascular endothelial growth factor]-targeted therapy," wrote David Quinn, MD, PhD, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and Primo Lara Jr, MD, University of California Davis Comprehensive Cancer Center, Sacramento.

Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus in the published CheckMate 025 trial; the most common adverse event with nivolumab was fatigue (in 2% of the patients).

The other most common side effects of nivolumab are cough, nausea, rash, difficulty dyspnea, diarrhea, constipation, decreased appetite, back pain, and arthralgia.

Nivolumab can also cause serious immune-mediated side effects in the lungs, colon, liver, kidneys, hormone-producing glands, and the brain.

The FDA granted the nivolumab in kidney cancer application priority review status on November 16 and has approved the drug 1 week later.

Renal cell carcinoma is the most common form of kidney cancer in adults, according to the FDA. The National Cancer Institute estimates 61,560 new cases and 14,080 deaths from kidney and renal pelvis cancer in the United States this year.


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