Immunotherapy treatment with nivolumab significantly improved survival among patients with recurrent or metastatic head and neck squamous cell carcinoma (SCCHN), according to interim analysis results of the phase III CheckMate-141 study presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, held April 16–20 in New Orleans.
Patients in the study assigned to nivolumab had a 30% reduction in the risk for death, and in those patients who were PD-L1 positive and p16-positive—a marker for human papillomavirus positivity—the risk for death was reduced by approximately half.
“Nivolumab is the first agent to demonstrate a significant improvement in overall survival in patients with SCCHN who progress after platinum-based therapy in a randomized, phase III comparative trial and fulfills an incredible unmet need in the clinic,” said Maura L. Gillison, MD, PhD, a professor in the department of internal medicine at the Ohio State University Comprehensive Cancer Center in Columbus, Ohio. “Nivolumab, therefore, represents a new standard of care option for patients with recurrent or metastatic SCCHN after platinum-based therapy.”
According to Gillison, about 50% of patients treated for SCCHN will have their disease recur within 3 to 5 years. SCCHN that recurs within 6 months is a particularly devastating disease with an average survival of less than 6 months, Gillison said.
The trial included 361 patients with SCCHN who had progressed within 6 months of receiving treatment with platinum-based chemotherapy. The patients were randomly assigned 2:1 to 3 mg/kg nivolumab every 2 weeks or weekly investigator’s choice consisting of single-agent chemotherapy with methotrexate, docetaxel, or cetuximab.
At the interim analysis, 55.4% of patients assigned nivolumab had died and 70.2% of patients assigned investigators choice had died. Patients assigned nivolumab had a 30% reduction in the risk for death compared with investigator’s choice (hazard ratio [HR], 0.70 [97.73% CI, 0.51-0.96]; P = .010). The median overall survival was more than 2 months longer for patients assigned the immunotherapy (7.5 vs 5.1 months; 95% CI, 4.0–6.0).
Although nivolumab demonstrated a survival benefit in the overall study population regardless of PD-L1 expression or p16 status, the researchers also evaluated overall survival by these two factors.
Compared with investigator’s choice, nivolumab resulted in a 45% reduction in the risk for death (HR, 0.55) in patients with PD-L1 of 1% or greater and an 11% reduction in patients with PD-L1 less than 1%. Similarly, nivolumab was associated with a 44% reduction in the risk for death in patients who were p16-positive and a 27% reduction in the risk for death in patients who were p16-negative.
According to Gillison, the frequency, type, and grade of toxicity was similar to what was seen in other clinical trial populations. More than half of patients (58.9%) experienced treatment-related adverse events of any grade while on nivolumab and 13.1% had grade 3/4 events. However, in patients assigned to investigator’s choice chemotherapy, 77.5% experienced treatment-related adverse events and 35.1% had a grade 3/4 event.