July 2015, Special ASCO Edition

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Encouraging Results for Pembrolizumab in Head and Neck Cancer

Immunotherapy

Pembrolizumab achieved “remarkable” results in a phase 1 study of previously treated, recurrent, squamous cell carcinoma of the head and neck.

Tumor shrinkage was observed in 57% of these poor-prognosis, heavily pretreated patients, and 24.8% had 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, 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 Seiwert, MD, Assistant Professor of Medicine and Associate HNC Program Leader at the University of Chicago, IL.

“Pembrolizumab was effective in both [human papillomavirus] HPV-positive and HPV-negative tumors, which is not typically seen in head and neck cancer,” he added.

Pembrolizumab is the first programmed death-1 (PD-1) inhibitor therapy to be approved for the treatment of melanoma by the FDA, and the immunotherapy is under study in head and neck, lung, bladder, and other tumors.

In the current era, median survival in previously treated recurrent/metastatic head and neck cancer is about 6 months. The standard of care for first-line therapy is platinum-based doublet chemotherapy with or without cetuximab. Second-line options are methotrexate, docetaxel, 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-1 ligand 1 (PD-L1) expression. The expansion cohort of KEYNOTE 012 included 132 patients unselected for PD-L1 expression treated at a fixed dose of pembrolizumab (infusion of 200 mg every 3 weeks) for 24 months or until disease progression or intolerable toxicity. Approximately 59% had received ?2 prior therapies.

Tumor shrinkage was reported in 57%. Overall objective response rate was 24.8%: 26.3% in HPV-negative patients and 20.6% in HPV-positive patients. About 25% of patients had stable disease, for a disease control rate of approximately 50%, which Seiwert called “remarkable” in this setting.

Duration of response is encouraging, and 86% of the responding patients remain in response at the time of data cutoff.

Pembrolizumab was better tolerated than aggressive chemotherapy and radiation, he said. About 60% of patients had an adverse event, and 15% reported fatigue. Other side effects included hypothyroidism (9.1%), decreased appetite (7.6%), and rash (7.6%).

Serious side effects occurred in fewer than 10% of patients. Four patients experienced serious immune-related adverse events that included pneumonitis (2 patients) and swelling of the face (2 patients).

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,” said Seiwert.

PD-L1 may be a biomarker to predict for benefit from pembrolizumab, he continued. 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 head and neck cancer.

Pembrolizumab is currently being compared with standard treatment in 2 ongoing phase 3 studies in patients with recurrent/metastatic head and neck cancer.

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