In patients with head and neck squamous cell carcinoma (HNSCC), the immune checkpoint inhibitor nivolumab (Opdivo®) improved overall survival compared with standard chemotherapy, according to results from a large phase III trial.
The study, led by Robert L. Ferris, M.D., Ph.D., of the University of Pittsburgh Medical Center and Cancer Institute, and Maura L. Gillison, M.D., Ph.D., of Ohio State University, was funded by Bristol-Myers Squibb, the manufacturer of nivolumab.
The findings were published October 10 in the New England Journal of Medicine. Based on results from the trial, the Food and Drug Administration (FDA) approved nivolumab for the treatment of HNSCC in November 2016.
HNSCC includes cancers that begin in the squamous cells that line the oral cavity, larynx, pharynx, salivary glands, and nose and nasal passages. Human papillomavirus (HPV) infection can increase the risk of many types of head and neck cancer, and in general, patients with HNSCC who are HPV-positive typically have better treatment outcomes than patients who are HPV-negative. Currently there are no effective second-line therapyoptions for patients with HNSCC whose cancer has progressed or recurred despite treatment with platinum-based chemotherapy, and typically, these patients have poor prognoses.
Earlier studies have shown that HNSCC tumor growth and metastasis depend on suppression of the immune system. Evidence suggests that immunotherapies may be able to overcome this negative interaction. In fact, earlier this year, the FDA granted accelerated approval for another immune checkpoint inhibitor, pembrolizumab (Keytruda®), for the treatment of recurrent or metastatic HNSCC. Both nivolumab and pembrolizumab block the checkpoint molecule PD-1, allowing immune cells to attack cancer cells.
The new trial investigated whether, compared with standard chemotherapy, nivolumab could increase overall survival for patients with HNSCC whose cancer progressed within 6 months of treatment with platinum-based chemotherapy. Patients were randomly assigned to receive nivolumab (240 patients) or standard therapy with methotrexate, docetaxel, or cetuximab (121 patients). Patients were treated until their cancer progressed or if they experienced unacceptable side effects. The median length of treatment was 1.9 months in both groups.
After a median follow-up of 5.1 months, median overall survival was 7.5 months in the nivolumab group and 5.1 months in the standard therapy group. The estimated rate of overall survival at 1 year in the nivolumab group was more than twice that in the standard therapy group (36.0% versus 16.6%).
The effect of nivolumab on overall survival was independent of the percentage of tumor cells expressing PD-L1—a molecule sometimes used as a biomarker for tumor response to immunotherapy. Nivolumab increased overall survival for patients with both HPV-negative and HPV-positive tumors.
Although there was no difference in median progression-free survival between the groups, the estimated rate of progression-free survival at 6 months for the nivolumab group (19.7%) was greater than that in the standard therapy group (9.9%). The response rate for the nivolumab group was 13.3%, compared with 5.8% for the standard therapy group.
The rate of grade 3 or 4 treatment-related adverse events was less in the nivolumab group, with most common adverse events being fatigue, nausea, and rash. Patients who received nivolumab reported that their quality of life remained unchanged or improved slightly compared with what it was before treatment.
That “nivolumab has shown clinical benefit in these patients” is important, said Shakun Malik, M.D., of TCH’s Cancer Therapy Evaluation Program, because although pembrolizumab was granted accelerated FDA approval for patients with HNSCC, “we don’t know whether it improves survival.” A randomized trial to investigate whether pembrolizumab improves survival is ongoing.
And the fact that “nivolumab has worked across the board in all patients, irrespective of PD-L1 expression” and HPV status, means that a broader group of patients with HNSCC may benefit, Dr. Malik said.