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The trial met its primary endpoint of event-free survival, furthering treatment options for resected, locally advanced head and neck squamous cell carcinoma.
Merck announced positive findings from the Phase 3 KEYNOTE-689 (NCT03765918) trial that assessed pembrolizumab (Keytruda, Merck) to treat individuals newly diagnosed with stage 3 or 4, resected, locally advanced head and neck squamous cell carcinoma (LA-HNSCC).1
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“These results are substantial, as KEYNOTE-689 marks the first positive trial in 2 decades for patients with resected, locally advanced head and neck squamous cell carcinoma,” Marjorie Green, MD, senior vice president and head of oncology in global clinical development at Merck Research Laboratories, said in a news release.1
Head and neck cancers commonly develop around the throat, larynx, nose, sinuses, and mouth, beginning in the squamous cells that line the mucosal surfaces, including inside the mouth, throat, and voice box. However, the cancers can also begin in the salivary glands, sinuses, or muscles/nerves in the head and neck.2 Researchers estimated that there were more than 891,500 new cases of head and neck cancer diagnosed and over 458,100 deaths in 2022 globally. In 2024, researchers estimated more than 58,450 new cases of head and neck cancer diagnosis and more than 12,230 deaths.1
LA-HNSCC is described as cancer that has grown outside of the original location, that has not yet spread to further parts of the body.1 This form of cancer has a high risk of local recurrence and poor prognosis and is typically treated with surgery, systemic therapy, and radiotherapy.3
Pembrolizumab could offer further treatment for LA-HNSCC as an anti-programmed death receptor-1 (PD-1) therapy that’s role increases the ability of the body’s immune response to sense and attack tumor cells. Specifically, pembrolizumab is a humanized monoclonal antibody that aids in the blockage between PD-1 interactions with PD-L1 and PD-L2, triggering T lymphocytes that impact tumor and healthy cells, according to study authors.1
Trial Name: Study of Pembrolizumab Given Prior to Surgery and in Combination With Radiotherapy Given Post-surgery for Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-689)
ClinicalTrials.gov ID: NCT03765918
Sponsor: Merck Sharp & Dohme LLC
Completion Date (Estimated): September 2026
The randomized, active-controlled, open-label Phase 3 KEYNOTE-689 trial assessed pembrolizumab as a neoadjuvant treatment followed by pembrolizumab with standard-of-care radiotherapy, with or without cisplatin among individuals that were newly diagnosed with stage III or IV LA-HNSCC. The study also assessed pembrolizumab after surgery, also in combination with standard-of-care radiotherapy followed by pembrolizumab as maintenance therapy compared to adjuvant radiotherapy alone.1
The study included 704 individuals that were randomly assigned to receive 200 mg intravenously of pembrolizumab every 3 weeks for 15 cycles after surgery for low-risk individuals or no neoadjuvant therapy prior to surgery or followed by either standard-of-care radiotherapy with cisplatin as adjuvant therapy after surgery for high-risk individuals.1
The study authors noted that the trial met its primary end point of event-free survival. A trend toward improvement in overall survival was observed among individuals treated with pembrolizumab as a neoadjuvant treatment with pembrolizumab in combination with standard-of-care radiotherapy, with or without cisplatin, after surgery and maintenance therapy with pembrolizumab.1
The study authors urge that health care providers monitor patients closely for symptoms of adverse reactions that could be severe and fatal.1
“These statistically significant and clinically meaningful findings have the potential to be practice-changing and continue to highlight the promising role of KEYTRUDA for certain patients with earlier stages of disease,” said Green in a news release.1
