Bristol-Myers Squibb Company announced that the US Food and Drug Administration (FDA) has approved Opdivo (nivolumab) injection, for intravenous use, 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.

Opdivo is the first and only immuno-oncology treatment proven in a phase 3 trial to significantly extend overall survival (OS) for these patients. In oncology clinical trials, OS is considered the gold standard primary endpoint to evaluate the outcome of any therapy.

The approval was based on results from the phase 3, CheckMate -141 trial in which Opdivo demonstrated statistically significant and clinically meaningful superior OS vs the comparator arm (investigator’s choice of methotrexate, docetaxel or cetuximab), with a 30% reduction in the risk of death (HR=0.70 [95% CI: 0.53-0.92; p=0.0101]). The median OS was 7.5 months (95% CI: 5.5-9.1) for Opdivo compared to 5.1 months (95% CI: 4.0-6.0) for investigator’s choice. Opdivo is associated with immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion reactions; and embryo-fetal toxicity.

“With this approval in head and neck cancer, we continue to lead the field in bringing our immuno-oncology science and the potential for increasing survival to more people with cancer,” said Chris Boerner, Head of U.S. Commercial, Bristol-Myers Squibb. “We take tremendous pride in the unprecedented speed and rigor with which we have brought Opdivo to market to address unmet needs across more tumor types than any other immuno-oncology treatment.”

Squamous cell carcinoma of the head and neck (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 higher potential for progression and recurrence. The relative five-year survival rate for metastatic head and neck cancers is <38%, and can be as low as 4% for recurrent or metastatic stage IV disease.

“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 Maura Gillison, M.D., Ph.D., lead investigator, Jeg Coughlin Chair of Cancer Research, The Ohio State University Wexner Medical Center. “This latest approval for Opdivo reinforces the potential to provide patients with improved overall survival, considered the gold standard in cancer care.”

Based on a pre-planned 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, the FDA granted Breakthrough Therapy Designation to Opdivo for recurrent or metastatic SCCHN after platinum-based therapy, underscoring the need for new treatment approaches for this disease. In October, the US National Comprehensive Cancer Network (NCCN) updated its clinical practice guidelines to recommend treatment with Opdivo 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. Opdivo has now been approved in five tumor types in under two years.

CheckMate -141 was a global phase 3, open-label, randomized, trial evaluating Opdivo versus investigator’s choice of therapy in patients with recurrent or metastatic SCCHN who had tumor progression during or within six months of receiving platinum-based therapy administered in the adjuvant, neo-adjuvant, primary (unresectable locally advanced) or metastatic setting. Patients were included regardless of their HPV or PD-L1 status. Patients were randomized 2:1 to receive Opdivo 3 mg/kg intravenously over 60 minutes every two weeks (n=240), or investigator’s choice (n=121) of: methotrextate 40 to 60 mg/m2 intravenously weekly, docetaxel 30 to 40 mg/m2 intravenously weekly, or cetuximab 400 mg/m2 intravenously once then 250 mg/m2 weekly. Therapies chosen for investigator’s choice represent the most commonly used therapies in the platinum refractory setting. The primary endpoint was OS. The trial’s secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).

In the trial, Opdivo demonstrated statistically significant superior OS with a 30% reduction in the risk of death (HR=0.70 [95% CI: 0.53-0.92; p=0.0101]), and a median OS of 7.5 months (95% CI: 5.5-9.1) for Opdivo compared to 5.1 months (95% CI: 4.0-6.0) for the investigator’s choice arm. There were no statistically significant differences between the two arms for PFS (HR=0.89; 95% CI: 0.70, 1.13) or ORR (13.3% [95% CI: 9.3, 18.3] vs 5.8% [95% CI: 2.4, 11.6] for Opdivo and investigator’s choice, respectively.1 Data from CheckMate -141 were published in The New England Journal of Medicine in October.

“We are excited to see the continued benefits of ongoing immuno-oncology research from a company with a long-standing commitment to head and neck cancer like Bristol-Myers Squibb,” said Brian Hill, oral cancer survivor and founder, The Oral Cancer Foundation. “Today’s approval provides hope for the thousands of previously treated SCCHN patients and their loved ones by bringing a new treatment option that has the potential to extend lives.”

The safety profile of Opdivo in CheckMate -141 was consistent with prior studies in patients with melanoma and non-small cell lung cancer. Opdivo was discontinued in 14% of patients and was delayed in 24% of patients for an adverse reaction.1 Serious adverse reactions occurred in 49% of patients receiving Opdivo. The most frequent serious adverse reactions reported in at least 2% of patients receiving Opdivo were pneumonia, dyspnea, aspiration pneumonia, respiratory failure, respiratory tract infection, and sepsis.

Cancers that are known as head and neck cancers usually begin in the squamous cells that line the moist mucosal surfaces inside the head and neck, such as inside the mouth and the throat. In 2016, approximately 64,000 new cases of head and neck cancer are estimated to be diagnosed in the US, resulting in more than 13,000 deaths. Head and neck cancers are more than twice as common among men as they are among women.