NIVOLUMAB APPROVED IN EUROPE FOR SQUAMOUS NSCLC

The first immunotherapy for the treatment of lung cancer has been approved in the Europe.

Specifically, the programmed cell death (PD) inhibitor nivolumab (Bristol-Myers Squibb Company) has been approved for the treatment of locally advanced or metastatic squamous non–small cell lung cancer (NSCLC) in patients who have already been treated with chemotherapy. Squamous NSCLC accounts for approximately 25% to 30% of all lung cancers.

The approval covers all 28 countries of the European Union (EU), where the drug will be marketed for use in lung cancer as NivolumabBMS. It is already marketed there for melanoma as Opdivo (the trade name used elsewhere in the world). The company said that it used two different trade names "in order to accelerate availability of nivolumab for health care professionals in both indications," but the goal is to have the two marketing authorizations "reconciled" under the trade name Opdivo by the end of 2015.

The approval is based on the phase 3 Checkmate-017 study, which was recently published in the New England Journal of Medicine and showed "unprecedented survival," as reported by Medscape Medical News.

This trial was conducted in patients with advanced SQ NSCLC who had experienced disease progression during or after one prior platinum doublet–based chemotherapy regimen. Nivolumab was compared with docetaxel (multiple brands) and showed a nearly double overall survival (OS) at 1 year vs chemotherapy (42% vs 24%; hazard ratio, 0.59; P = .0002). The median OS was 9.2 months with nivolumab vs 6 months with docetaxel.

The company noted that survival benefit was observed independently of PD-L1 expression across all prespecified expression levels (1%, 5%, and 10%).

The safety profile of nivolumab was "favorable" when compared with docetaxel, the company noted. Treatment-related adverse events (AEs) occurred less frequently with nivolumab (any grade, 58%; grade 3-4, 6.9%; no grade 5 events) than with docetaxel (any grade, 86%; grade 3-5, 55%; grade 5, 2.3%), including both hematologic and nonhematologic toxicities. Treatment-related AEs led to discontinuation in 3.1% of patients in the nivolumab arm compared with 10.1% for docetaxel. Pneumonitis (1.5%) was the most common treatment-related AE leading to discontinuation in the nivolumab arm; for the docetaxel arm, it was peripheral neuropathy (3.1%).

When this trial was presented at the annual meeting of the American Society of Clinical oncology meeting earlier this year, it was hailed by lung cancer experts as practice changing.

Nivolumab is the new standard of care for patients with previously treated squamous NSCLC, declared Roy Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center, in New Haven, Connecticut, who acted as discussant for the study. OS was significantly improved, and nivolumab showed significantly less toxicity than docetaxel, he said.

"We now need to move this to frontline therapy in lung cancer," Dr Herbst said.

"Today's approval of nivolumab for squamous non–small cell lung cancer is truly a major advance for patients fighting this devastating disease, and the providers that treat them," said Rolf Stahel, MD, president of the European Society of Medical Oncology and professor at University Hospital Zurich, in Germany. "Nivolumab has shown statistically significant and clinically meaningful improvement in efficacy vs standard of care in this patient population. This approval reinforces the science behind immuno-oncology, including our understanding of the role of PD-L1 expression."

Also Benefit in Renal Cancer

Just announced is the news that nivolumab has shown a survival benefit in patients with metastatic renal cell carcinoma in the phase 3 CheckMate-025 trial. The company said that this trial was stopped early because an assessment conducted by the independent data monitoring committee concluded that the study met its end point, demonstrating superior OS in patients receiving nivolumab compared with those receiving everolimus (Afinitor, Novartis Pharmaceuticals Company) in the control arm.