KEYNOTE-689 Trial of Pembrolizumab Shows Promising EFS in LA-HNSCC

Ravindra Uppaluri, MD, PhD, chief of head and neck surgery at the Dana-Farber Brigham Cancer Center, and chief of the otolaryngology group at the Brigham and Women's Hospital, discusses the findings from the phase 3 KEYNOTE-689 (NCT03765918) trial of pembrolizumab (Keytruda) in patients with newly diagnosed, resectable, locally advanced head and neck squamous cell carcinoma (LA-HNSCC).

“The primary end point was looking at event-free survival [EFS]. First of all, the statistical design was a little bit complicated but done in what is called a sequential strategy, where patients were first looked at based on the [combined positive score (CPS)] , and that is what the initial stratification was,” explains Uppaluri.

Data presented at the 2025 AACR Annual Meeting showed that for the primary end point of the study, EFS, rates were significantly higher in the pembrolizumab arm at 51.8 months vs 30.4 months in the control group. Secondary end points of the study included pathological response and overall survival, with the latter showing no significant difference.

“Ultimately, what we found was that EFS was tested and found positive for all patients in the experimental arm compared with the standard of care. It showed that the median event-free survival across all patients was 51.8 months in the pembrolizumab arm vs 30.4 months after a median of 38.3 months of follow-up. This is a significant difference, going from 51.8 months to 30.4 months in terms of event-free survival in these patients, and was really the most exciting part of the study,” adds Uppaluri.

The trial emphasized the importance of multidisciplinary care and suggested future studies on the optimal timing of pembrolizumab administration.

In February 2025, topline findings from a prespecified first interim analysis of the phase 3 KEYNOTE-689 trial provided the basis for an FDA supplemental biologics license application (sBLA) for pembrolizumab (Keytruda).1,2 In patients with resectable LA-HNSCC, the perioperative treatment regimen of pembrolizumab led to a statistically significant and clinically meaningful improvement in EFS. A Prescription Drug User Fee Act target action date for the application has been set for June 23, 2025, by the FDA.

REFERENCES:

1. FDA grants priority review to Merck’s application for KEYTRUDA® (pembrolizumab) plus standard of care as perioperative treatment for resectable locally advanced head and neck squamous cell carcinoma. News release. Merck. February 25, 2025. Accessed April 22, 2025. https://tinyurl.com/2kmefvjn

2. 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 April 22, 2025. https://tinyurl.com/86vmtmad