Merck's Keytruda (pembrolizumab) Achieves Primary Goal of Event-Free Survival (EFS) in Perioperative Treatment for Patients with Resected Locally Advanced Head and Neck Squamous Cell Carcinoma
The KEYNOTE-689 trial has become the first Phase 3 study to show a statistically significant and clinically meaningful improvement in event-free survival (EFS) for patients receiving anti-PD-1 therapy in the early stages of head and neck squamous cell carcinoma (HNSCC).
Merck has announced that the Phase 3 KEYNOTE-689 study evaluating Keytruda (pembrolizumab), their anti-PD-1 therapy, as a perioperative treatment for patients newly diagnosed with stage III or IVA resected locally advanced head and neck squamous cell carcinoma (LA-HNSCC) has successfully met its primary endpoint of EFS.
In the trial, Keytruda was administered as neoadjuvant therapy prior to surgery and continued post-surgery alongside standard-of-care radiotherapy (with or without cisplatin) as adjuvant therapy, followed by Keytruda for maintenance. This regimen was compared to adjuvant radiotherapy (with or without cisplatin) alone. A pre-determined interim analysis conducted by an independent Data Monitoring Committee revealed a significant and clinically relevant improvement in EFS for patients treated with the Keytruda perioperative regimen.
Additionally, the trial demonstrated a statistically significant improvement in major pathological response (mPR), a key secondary endpoint, for patients receiving Keytruda compared to those who received only adjuvant radiotherapy. The safety profile of Keytruda was consistent with previously reported studies, with no new safety concerns identified.
A trend toward better overall survival (OS), another key secondary outcome, was also observed in patients treated with Keytruda as a neoadjuvant therapy, followed by radiotherapy (with or without cisplatin) and maintenance therapy. However, OS results did not reach statistical significance in patients with a PD-L1 Combined Positive Score (CPS) of 10 or higher in this first interim analysis. Due to the study's hierarchical statistical testing approach, formal OS testing was not conducted in patients with CPS ≥1 or the broader intent-to-treat (ITT) population. OS outcomes will be revisited in the next interim analysis.
The trial results are set to be presented at an upcoming medical conference and will be submitted to health authorities for review.
Currently, Keytruda is approved as a standalone treatment or in combination therapies for patients with metastatic, unresectable, or recurrent head and neck squamous cell carcinoma (HNSCC) across the U.S., Europe, China, Japan, and other countries globally.
About the KEYNOTE-689 Study
KEYNOTE-689 is a Phase 3, randomized, open-label, and active-controlled clinical trial (NCT03765918) evaluating the use of Keytruda as a neoadjuvant therapy followed by post-surgical treatment with Keytruda and radiotherapy (with or without cisplatin) as adjuvant therapy, then continuing with Keytruda for maintenance. The trial involved newly diagnosed, stage III or IVA, treatment-naive patients with resected locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The efficacy of the treatments was assessed based on PD-L1 CPS status. The study's primary goal was event-free survival (EFS), while secondary goals included overall survival (OS), major pathological response (mPR), complete pathological response, and safety.
Approximately 704 patients were enrolled in the study and randomly assigned to one of two treatment groups (1:1). The first group received Keytruda (200 mg IV every three weeks for two cycles) as a neoadjuvant therapy, followed by post-surgical Keytruda (200 mg IV every three weeks for 15 cycles) combined with standard-of-care radiotherapy, with or without cisplatin, based on patient risk. The second group did not receive any neoadjuvant therapy, undergoing only post-surgical radiotherapy with or without cisplatin.
About Head and Neck Cancer
Head and neck cancer refers to a variety of tumors that form in the areas around the throat, larynx, nose, sinuses, and mouth. Most cases of head and neck cancer are squamous cell carcinomas, which originate in the thin, flat cells that line the surface of these structures. Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) refers to cancer that has extended beyond its original site but has not spread to distant parts of the body. The primary risk factors for head and neck cancer include tobacco use, alcohol consumption, and human papillomavirus (HPV) infection.
Globally, it was estimated that over 891,500 new cases of head and neck cancer were diagnosed, with over 458,100 deaths in 2022. In the United States, projections indicate that there will be more than 58,450 new diagnoses of head and neck cancer, resulting in over 12,230 deaths in 2024.
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