KEYNOTE-689 Study: Ongoing Follow-up and Anticipated Overall Survival Data

On Thursday, June 12, 2025, the FDA approved perioperative pembrolizumab (Keytruda) in head and neck squamous cell carcinoma (HNSCC). In an interview with Targeted Oncology^TM, Douglas Adkins, MD, professor in the Division of Oncology at Washington University in St. Louis, discussed the future direction of the KEYNOTE-689 study (NCT03765918) that supported the approval.

The KEYNOTE-689 trial demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS), the trial’s primary end point, in the perioperative pembrolizumab arm compared with the SOC arm. For patients whose tumors express PD-L1 CPS ≥1 (n = 682), the median EFS was 59.7 months (95% CI, 37.9 to not reached [NR]) for those given pembrolizumab vs 29.6 months (95% CI, 19.5-41.9) for those in the control arm (HR, 0.70; 95% CI, 0.55-0.89]; P =.00140).

The KEYNOTE-689 trial is continuing its follow-up phase to explore whether an improvement in overall survival (OS) will be observed over time. The timing of this OS readout is event-driven and currently unknown, but it represents a crucial endpoint that we eagerly anticipate. Investigators are specifically looking to determine if there is a statistically significant improvement in OS for the arm receiving pembrolizumab plus standard care compared to the standard care alone.

In Adkins's opinion, the emerging data from this trial provides strong justification for considering an alteration to the current standard of care for patients with resectable advanced head and neck cancer.

REFERENCE:

FDA approves neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck squamous cell carcinoma. FDA. June 12, 2025. Accessed June 13, 2025. https://tinyurl.com/47aztrcp