FDA Approves Perioperative Keytruda for Locally Advanced Head and Neck Cancer

Keytruda was approved for locally advanced head and neck cancer before and after surgery: © stock.adobe.com.

The U.S. Food and Drug Administration (FDA) approved Keytruda (pembrolizumab) for adults with resectable locally advanced head and neck squamous cell carcinoma that expresses PD-L1 (combined positive score of 1 or higher). The therapy is given alone before surgery, then with radiation with or without cisplatin after surgery, followed by Keytruda alone.

According to the FDA, this is the first approval for head and neck squamous cell carcinoma in six years and the first overall perioperative approval for locally advanced head and neck squamous cell carcinoma.

Efficacy was evaluated in the KEYNOTE-689 trial, an open-label, multicenter study of 714 patients with resectable, locally advanced stage 3 or 4A head and neck squamous cell carcinoma.

For patients whose tumors expressed PD-L1 with a combined positive score of 1 or higher (682 patients), median event-free survival was 59.7 months in the Keytruda group and 29.6 months in the control group. Event-free survival was defined as the time from randomization to disease progression that prevented definitive surgery, local or distant progression or recurrence, or death from any cause. Overall survival results were still immature, with 76% of the planned deaths reported, but no trend toward harm was seen.

Among patients who received neoadjuvant Keytruda, 1.4% were unable to undergo surgery due to side effects, compared with 1.4% in the control group.

The prescribing information for Keytruda includes warnings and precautions for immune-related side effects, infusion-related reactions, and potential harm to unborn babies. Side effects seen in this trial were consistent with what has been previously reported with Keytruda.

The recommended Keytruda dose is 200 milligrams (mg) every three weeks or 400 mg every six weeks. When given on the same day as chemotherapy, Keytruda should be given first.

This review was part of Project Orbis, which helps speed up access to cancer treatments in multiple countries. The FDA also used a priority review process to evaluate the application more quickly.

"The standard of care for patients with resectable locally advanced head and neck squamous cell carcinoma has remained the same for over two decades, representing a significant unmet need for new treatment options,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, in a news release from Merck, Keytruda’s manufacturer. “Based on the compelling results of the KEYNOTE-689 trial, we hope to reduce the risk of recurrence and disease progression in earlier stages of disease. We look forward to working with the FDA to potentially bring Keytruda to these patients as soon as possible.”

The application was supported by findings from the phase 3 KEYNOTE-689 trial. In the trial, patients with resectable locally advanced head and neck squamous cell carcinoma who received perioperative Keytruda experienced a statistically significant and clinically meaningful improvement in event-free survival compared with those who received adjuvant radiotherapy with or without chemotherapy.

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