Merck’s KEYTRUDA® Achieves EFS Primary Endpoint in Perioperative Treatment for Resected Head and Neck Cancer

On October 8, 2024, Merck announced results from their Phase 3 KEYNOTE-689 trial, which evaluated the efficacy of KEYTRUDA® (pembrolizumab) as a perioperative treatment for patients with newly diagnosed stage III or IVA, resected, locally advanced head and neck squamous cell carcinoma (LA-HNSCC). KEYNOTE-689 is notable for being the first Phase 3 trial to show a statistically significant and clinically meaningful improvement in event-free survival (EFS) for an anti-PD-1 therapy in earlier stages of this cancer type.

The study assessed the use of KEYTRUDA as a neoadjuvant treatment before surgery, followed by its use in combination with standard-of-care radiotherapy (with or without cisplatin) as adjuvant therapy, and then continued as maintenance therapy. This approach was compared to the standard-of-care adjuvant radiotherapy (with or without cisplatin) alone. The findings from a pre-specified first interim analysis, conducted by an independent Data Monitoring Committee, revealed that the patients treated with the KEYTRUDA regimen experienced a significant improvement in EFS. Additionally, there was a notable improvement in major pathological response (mPR), a key secondary endpoint, for those in the KEYTRUDA arm compared to those who received adjuvant radiotherapy alone. The safety profile for KEYTRUDA remained consistent with previous studies, with no new safety concerns identified.

Dr. Marjorie Green, senior vice president and head of oncology at Merck Research Laboratories, highlighted the significance of these findings, noting that KEYNOTE-689 represents the first positive trial in two decades for patients with resected, locally advanced head and neck squamous cell carcinoma. She emphasized that these results could potentially change clinical practice, underscoring the promising role of KEYTRUDA for patients with earlier stages of this disease.

A trend towards improved overall survival (OS) was also observed with KEYTRUDA in combination with standard-of-care radiotherapy and as maintenance therapy. However, the OS results did not reach statistical significance in patients whose tumors had a PD-L1 Combined Positive Score (CPS) of 10 or higher at this first interim analysis, and formal testing for OS was not conducted in the CPS ≥1 and intention-to-treat (ITT) populations due to the statistical testing hierarchy. OS outcomes will be assessed in the next interim analysis.

The results of the study will be presented at an upcoming medical meeting and submitted to regulatory authorities. Currently, KEYTRUDA is approved as a monotherapy and in combination therapies for various patients with metastatic or unresectable, recurrent HNSCC in multiple regions, including the U.S., Europe, China, and Japan.

The KEYNOTE-689 trial is a randomized, active-controlled, open-label Phase 3 study that enrolled approximately 704 patients. These patients were randomized to receive either the KEYTRUDA treatment regimen or the standard-of-care adjuvant radiotherapy. The primary endpoint of the study is EFS, with secondary endpoints including OS, mPR, pathological complete response, and safety.

Head and neck cancer encompasses various tumors that develop in or around the throat, larynx, nose, sinuses, and mouth. Most of these cancers are squamous cell carcinomas. 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. Key risk factors for developing head and neck cancer include tobacco and alcohol use, as well as human papillomavirus (HPV) infection. In 2022, there were more than 891,500 new cases of head and neck cancer and over 458,100 deaths globally. In the U.S. alone, there are expected to be over 58,450 new cases and more than 12,230 deaths from head and neck cancer in 2024.

Merck's focus on early-stage cancer research is aimed at improving long-term survival rates by detecting and treating cancers at their most treatable stages. Building on the established efficacy of KEYTRUDA in advanced cancers, Merck is conducting numerous studies to explore its potential in earlier stages of various cancers.