Chicago, IL—Pembrolizumab (Keytruda) achieved “remarkable” results in a phase 1 study of previously treated patients with recurrent, squamous-cell carcinoma of the head and neck, according to presenters at the 2015 American Society of Clinical Oncology (ASCO) annual meeting.
Tumor shrinkage was observed in 57% of these heavily pretreated patients with poor prognosis, and 24.8% had a partial or complete response on treatment with pembrolizumab in an expansion cohort of the phase 1 KEYNOTE 012 trial.
“This is the largest experience of immunotherapy in head and neck cancer. Pembrolizumab was twice as effective as we have seen with standard therapy with cetuximab [Erbitux], the only approved targeted therapy for this cancer. Responses are durable, which has not been seen before in head and neck cancer,” said lead author Tanguy Y. Seiwert, MD, Assistant Professor of Medicine and Associate Head and Neck Cancer Program Leader at the University of Chicago.
“Pembrolizumab was effective in both HPV-positive and HPV-negative tumors, which is not typically seen in head and neck cancer,” he added.
Pembrolizumab is the first anti–PD-1 therapy to be approved by the FDA for the treatment of melanoma, and this immunotherapy is under study in head and neck, lung, bladder, and other cancers.
In the current era, the median survival in previously treated recurrent or metastatic head and neck cancer is approximately 6 months. The standard of care for first-line therapy is platinum-based doublet chemotherapy with or without cetuximab. The second-line options are methotrexate (Trexall), docetaxel (Taxotere), and cetuximab.
In the first phase of KEYNOTE 012, pembrolizumab achieved a response rate of 20% at a dose of 10 mg/kg every 2 weeks in patients enriched for PD ligand 1 (PD-L1) expression. The expansion cohort of KEYNOTE 012, the results of which were presented at ASCO, included 132 patients who were unselected for PD-L1 expression and received a fixed dose of pembrolizumab (infusion of 200 mg every 3 weeks) for 24 months or until disease progression or intolerable toxicity. Approximately 59% of the patients had received ≥2 previous therapies.
Tumor shrinkage was reported in 57% of the patients. The overall objective response rate was 24.8%, and was 26.3% in HPV-negative patients and 20.6% in HPV-positive patients. Approximately 25% of patients had stable disease, for a disease control rate of approximately 50%, which Dr Seiwert called “remarkable” in this setting.
The duration of response in responders was encouraging, and 86% of the responding patients were still responding at the time of the ASCO meeting.
Pembrolizumab was better tolerated than aggressive chemotherapy and radiation, he said, with approximately 60% of patients having any adverse event, and 15% reporting fatigue. Other side effects included hypothyroidism (9.1%), decreased appetite (7.6%), and rash (7.6%).
Serious side effects occurred in <10% of patients. A total of 4 patients experienced serious immune-related adverse events that included 2 patients with pneumonitis and 2 with swelling of the face.
Longer follow-up is needed to assess survival. As has been seen with other immunotherapies, “Some patients who have any degree of response or even disease progression at the beginning of therapy may ultimately benefit and have a survival improvement,” Dr Seiwert noted.
PD-L1 may be a biomarker to predict for benefit from pembrolizumab, he continued. The analysis of PD-L1 status and response is ongoing in this trial. The optimal cutoff for PD-L1 expression and the clinical utility of this biomarker have yet to be determined in patients with head and neck cancer.
Pembrolizumab is currently being compared with standard treatment in 2 ongoing phase 3 studies in patients with recurrent or metastatic head and neck cancer.