Perioperative Pembrolizumab Betters Survival in Stage III/IV Head and Neck Cancer

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Perioperative pembrolizumab (Keytruda) led to improved event-free survival (EFS) in patients with stage III or IVA, resected head and neck squamous cell carcinoma (HNSCC), meeting the primary end point of the phase 3 KEYNOTE-689 study (NCT03765918).¹

“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,” said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, in a press release. “These statistically significant and clinically meaningful findings have the potential to be practice-changing and continue to highlight the promising role of [pembrolizumab] for certain patients with earlier stages of disease.”

A trend toward improved overall survival (OS), a key secondary end point, was also observed. At this analysis, the OS results did not reach statistical significance in patients with a PD-L1 combined positive score (CPS) of 10 or greater. OS will be evaluated at the next interim analysis.

Full results from KEYNOTE-689 will be presented at an upcoming medical meeting and shared with regulatory authorities.

Pembrolizumab is currently approved in combination with platinum and fluorouracil for the first-line treatment of metastatic or unresectable, recurrent HNSCC; as a single-agent for first-line treatment of unresectable, recurrent HNSCC with a positive CPS; and as a single-agent for recurrent or metastatic HNSCC with disease progression following platinum-containing chemotherapy.

About KEYNOTE-689

The randomized, active-controlled, open-label, phase 3 study is evaluating pembrolizumab as neoadjuvant therapy, followed by pembrolizumab plus standard-of-care radiotherapy (with or without cisplatin) as adjuvant therapy, and then as maintenance for patients with newly diagnosed stage III/IVA HNSCC.

An estimated 704 patients were enrolled in the study across 192 global sites.^1,2 The study’s primary end point is EFS, and secondary end points include major pathological response, OS, pathological complete response, and incidence of adverse events.²

Patients with histologically confirmed, resectable, nonmetastatic HNSCC with evaluable tumor burden based on RECIST v1.1 and results from human papillomavirus testing defined as p16 were eligible for enrollment. Patients were also required to have an ECOG performance status of 0 or 1 within 10 days of randomization. Those who previously received an anti–PD-1 or anti–PD-L1 agent or radiotherapy, with diagnosis of immunodeficiency or receiving immunosuppressive therapy, who had a known additional malignancy, or who had an active autoimmune disease were not eligible for enrollment.

The study has an estimated completion date of September 10, 2026.

REFERENCES:

1. Merck’s KEYTRUDA® (pembrolizumab) met primary endpoint of event-free survival (EFS) as perioperative treatment regimen in patients with resected, locally advanced head and neck squamous cell carcinoma. News release. Merck. October 8, 2024. Accessed October 8, 2024. https://tinyurl.com/e8neub5t

2. 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. Updated April 16, 2024. Accessed October 8, 2024. https://clinicaltrials.gov/study/NCT03765918