Abstract
In patients with head and neck squamous cell carcinoma refractory to platinum-based chemotherapy, those treated with nivolumab had a 30% reduction in the risk of death compared with those assigned to receive one of three single-agent chemotherapies, according to a recent phase III trial. In addition, 1-year survival among nivolumab recipients was double that of those who received a chemotherapeutic, the current standard of care.
For patients with head and neck squamous cell carcinoma (HNSCC) that progresses or recurs within 6 months of platinum-based chemotherapy, the prognosis is bleak: The disease progresses so rapidly that their average survival is barely 6 months. However, in a recent phase III trial of the PD-1 checkpoint blocker nivolumab (Opdivo; Bristol-Myers Squibb), 1-year patient survival was double that of patients who received single-agent chemotherapy, the current standard of care.
Results of the study were presented at last month's American Association for Cancer Research Annual Meeting 2016 in New Orleans, LA.
Researchers enrolled 361 patients in the trial, randomly assigning 240 of them to receive nivolumab and the rest to receive a standard therapy of the investigator's choice—docetaxel, methotrexate, or cetuximab. At the interim analysis, patients assigned to nivolumab had a 30% reduction in risk of death compared with those assigned to a therapy of the investigator's choice, with median overall survival of 7.5 months versus 5.1 months, respectively.
“What we think is most important about this trial is the proportion of patients who survived to a year—it doubled with nivolumab therapy in comparison to investigator's choice,” said Maura Gillison, MD, PhD, a professor in the Department of Internal Medicine at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute in Columbus, who presented the study's results. “It was 36.0% versus 16.6%, for a 20% absolute improvement in the number of patients who survived to a year, something that has never been seen in this patient population before.”
Because certain types of HNSCC have been linked to human papillomavirus (HPV) infection, the researchers checked the HPV status of patients' tumors. In addition, they assessed tumor cells' PD-L1 expression, a potential biomarker for response. They noted improved survival in every group of patients who received nivolumab—HPV-positive, HPV-negative, PD-L1 expression in more than 1% of tumor cells, and PD-L1 expression in less than 1% of tumor cells—compared with chemotherapy. However, the benefit was greatest in patients whose tumors were HPV-positive and had PD-L1 expression greater than 1%. “In those two groups, the risk of death was reduced by approximately half,” said Gillison.
Regarding side effects, no new or unexpected toxicities were observed. Among patients who received nivolumab, 58.9% experienced at least one side effect, compared with 77.5% of those who received a therapy of the investigator's choice. In terms of serious side effects, the data again favored nivolumab over investigator's choice—13.1% and 35.1%, respectively.
“All practicing oncologists who take care of head and neck patients are going to take notice of this study,” said Raymond DuBois, MD, PhD, dean of the Medical University of South Carolina College of Medicine in Charleston.
“These patients have unbelievable functional problems with things we all take for granted—speech, swallowing, chewing, communicating, breathing—and their disease progresses quite rapidly,” added Gillison, noting that she has treated only patients with head and neck cancer for 20 years. “This is the first time in my career where I've had an agent [that improves survival and quality of life] to reach for in this patient population.” –Suzanne Rose