FDA Expands Opdivo Indications to Include Head-and-Neck Cancer

Treatment extends overall survival compared with methotrexate, docetaxel, or cetuximab

The FDA has given the nod to nivolumab (Opdivo, Bristol-Myers Squibb) for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy. Nivolumab is the only immuno-oncology treatment shown in a phase 3 trial to significantly extend overall survival (OS) for these patients. In oncology clinical studies, OS is considered the “gold standard” primary endpoint to evaluate the outcome of any therapy.

Nivolumab was previously approved for use in patients with non–small-cell lung cancer, metastatic melanoma, renal cell carcinoma, or classical Hodgkin lymphoma.

The FDA’s decision was based on results from the CheckMate-141 trial, a global phase 3, open-label, randomized study comparing nivolumab with the investigators’ choice of therapy (methotrexate, docetaxel, or cetuximab) in patients with recurrent or metastatic SCCHN who had experienced tumor progression within six months of receiving platinum-based therapy administered in the adjuvant, neoadjuvant, primary (unresectable locally advanced), or metastatic setting. Patients were included in the study regardless of their human papillomavirus or programmed death ligand-1 (PD-L1) status.

The patients were randomly assigned to receive nivolumab 3 mg/kg intravenously over 60 minutes every two weeks (n = 240) or the investigators’ choice of therapy (n = 121), which consisted of intravenous (IV) methotrextate 40 to 60 mg/m2 weekly; IV docetaxel 30 to 40 mg/m2 weekly; or IV cetuximab 400 mg/m2 once and then 250 mg/m2 weekly. The drugs selected for the investigators’ choice represented the most commonly used therapies in the platinum-refractory setting. The study’s primary endpoint was OS. Secondary endpoints included progression-free survival (PFS) and the objective response rate (ORR).

Nivolumab demonstrated significantly superior OS compared with the investigators’ choice of therapy, with a 30% reduction in the risk of death (hazard ratio [HR], 0.70; P = 0.0101) and a median OS of 7.5 months compared with 5.1 months, respectively. There were no statistically significant differences between the two treatment arms for PFS (HR, 0.89) or ORR (13.3% vs 5.8%). The results were published in October in the New England Journal of Medicine.

In April 2016, the FDA granted a breakthrough therapy designation to nivolumab for the treatment of patients with recurrent or metastatic SCCHN after platinum-based therapy.

SCCHN accounts for more than 90% of all head-and-neck cancers, and more than 50% of SCCHN patients present with stage III or higher disease (locally advanced or metastatic), which has a greater potential for progression and recurrence. The relative five-year survival rate for patients with metastatic head-and-neck cancers is less than 38% and can be as low as 4% for patients with recurrent or metastatic stage IV disease.

Treatment with nivolumab is associated with immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, renal dysfunction, skin adverse reactions, encephalitis, infusion reactions, and embryofetal toxicity.

Source: Bristol-Myers Squibb; November 10, 2016.