Perioperative Pembrolizumab Enhances Outcomes in Newly Diagnosed Head and Neck Cancer Patients: Results from a Clinical Trial

A recent Phase III clinical trial has demonstrated that adding pembrolizumab, an immunotherapy drug known as Keytruda, before and after surgery significantly improves outcomes for patients with newly diagnosed, locally advanced head and neck squamous cell carcinoma (HNSCC). The trial, presented at the AACR Annual Meeting 2025, involved 714 patients with stage 3–4 HNSCC across various locations including the larynx, hypopharynx, and oral cavity. All participants initially underwent surgery followed by adjuvant therapy tailored to pathology results, with 363 patients receiving pembrolizumab in the perioperative period. The primary measure of success was event-free survival, which indicates the time until recurrence or death, while secondary outcomes included the rate of major pathologic response (mPR), defined as at least 90% tumor reduction, and overall survival. Results showed that patients treated with pembrolizumab had at least a 27% reduction in recurrence risk, with improved mPR rates, especially among tumors expressing high levels of PD-L1. Tumors with a PD-L1 combined positive score of 10 or more not only had a higher likelihood of significant tumor reduction but also a 34% decrease in recurrence. The therapy was generally well-tolerated, with similar rates of severe adverse events in both study groups. Notably, the study highlights the transformative potential of integrating immunotherapy into standard surgical treatment to improve prognosis in head and neck cancer. These findings suggest that perioperative use of pembrolizumab could redefine treatment guidelines, offering new hope for patients facing this challenging disease. Moving forward, researchers aim to optimize this approach and explore modifications to surgery and adjuvant therapy to further minimize side effects and enhance long-term outcomes.