Nivolumab Approved for Squamous Cell Carcinoma of the Head and Neck

The US Food and Drug Administration (FDA) in record time has approved nivolumab (Opdivo) for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after a platinum-based therapy. 

On November 10, 2016, the FDA approved this agent based on data from an international, multicenter, open-label, randomized trial (CheckMate 141) comparing nivolumab with investigator’s choice (IC) of chemotherapy with cetuximab (Erbitux), methotrexate, or docetaxel. All the patients had recurrent or metastatic SCCHN with disease progression on or within 6 months of receiving platinum-based chemotherapy.

The trial enrolled 361 patients randomized to nivolumab 3 mg/kg every 2 weeks intravenously (IV) or IC of either cetuximab 400 mg/m² IV once, then 250 mg/m2 IV weekly, methotrexate 40 mg/m² IV weekly, or docetaxel 30 mg/m² IV weekly until disease progression or unacceptable toxicity. There were 240 patients in the nivolumab arm and 121 patients in the IC arm.

The trial demonstrated a statistically significant and clinical improvement in overall survival (OS) associated with the nivolumab arm (hazard ratio, 0.7). The estimated median OS was 7.5 months in the nivolumab arm and 5.1 months for IC.

“Squamous cell carcinoma of the head and neck that progresses on or after platinum-based therapy is a debilitating and hard-to-treat disease associated with a very poor prognosis,” said lead study investigator Maura Gillison, MD, PhD, who is with Ohio State University Wexner Medical Center, Columbus, Ohio. “This latest approval for Opdivo reinforces the potential to provide patients with improved overall survival, considered the gold standard in cancer care.”

Serious adverse reactions occurred in 49% of patients receiving nivolumab. Nivolumab was discontinued in 14% of patients and was delayed in 24% of patients for an adverse reaction. The most frequent serious adverse reactions reported in at least 2% of patients receiving nivolumab were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis.

The most common adverse reactions occurring in more than 10% of nivolumab-treated patients and at a higher incidence than IC were cough and dyspnea. Laboratory abnormalities were also noted in 10% of patients receiving nivolumab, such as elevated alkaline phosphatase, amylase, TSH, calcium, and potassium.

Based on a preplanned interim analysis, CheckMate 141 was stopped early in January 2016 because an assessment conducted by the independent Data Monitoring Committee concluded the study met its primary endpoint of OS.  In April 2016, this agent was granted Breakthrough Therapy Designation for recurrent or metastatic SCCHN after platinum-based therapy.  In October, the US National Comprehensive Cancer Network (NCCN) updated its clinical practice guidelines to recommend treatment with nivolumab as the only category 1 single-agent therapy for patients with recurrent or metastatic head and neck cancer with disease progression on or after platinum-containing chemotherapy.

Nivolumab has now been approved in five tumor types in less than 2 years.