Merck's Keytruda Breaks New Ground in Head and Neck Cancer Treatment

Merck & Co.'s blockbuster immunotherapy drug Keytruda (pembrolizumab) has achieved a significant milestone in the treatment of head and neck cancer. The U.S. Food and Drug Administration (FDA) has granted breakthrough approval for Keytruda as the first immunotherapy to be used in a perioperative setting for resectable locally advanced head and neck squamous cell carcinoma (HNSCC). This approval marks a potential paradigm shift in the management of this challenging disease.

FDA Approval Details and Clinical Trial Results

The FDA's decision is based on data from the phase 3 Keynote-689 trial, which demonstrated Keytruda's efficacy when used both before and after surgery in combination with standard-of-care treatments. In patients with PD-L1-positive tumors, Keytruda reduced the risk of disease recurrence, progression, or death by 30% compared to standard postsurgical treatment alone.

Patients receiving Keytruda showed a median event-free survival of 59.7 months, more than doubling the 29.6 months observed in the control arm. This significant improvement in outcomes underscores the potential of immunotherapy in earlier stages of cancer treatment.

However, the approval comes with a notable limitation. The perioperative use of Keytruda is restricted to patients whose tumors express PD-L1 at a combined positive score of at least 1. This limitation has raised questions about the treatment's applicability to the broader HNSCC patient population.

Expert Perspectives and Future Implications

Dr. Ravindra Uppaluri, principal investigator of the Keynote-689 trial from Brigham and Women's Hospital and the Dana-Farber Cancer Institute, hailed the approval as a "potentially significant shift" in HNSCC management. However, he argued for broader application of Keytruda in this setting, noting that PD-L1-negative cases comprise only about 5% of patients in this HNSCC population.

The approval's impact extends beyond U.S. borders. Under the FDA's Project Orbis, concurrent reviews of Keytruda for this indication are underway in Israel, Canada, Australia, Singapore, Brazil, and Switzerland. European and Japanese regulatory authorities are also independently evaluating the drug for similar approval.

This latest development adds to Keytruda's growing list of indications in HNSCC. The drug is already approved in combination with chemotherapy for first-line treatment of metastatic or unresectable recurrent HNSCC, regardless of PD-L1 status. It is also approved as a single agent for first-line HNSCC in PD-L1-positive tumors.

As the pharmaceutical industry continues to advance immunotherapy applications, Merck's success with Keytruda in head and neck cancer represents a significant step forward in expanding treatment options for patients with this challenging disease.