KEYNOTE-689 Results Provide “Foundation” for Alternative HNSCC Strategies

Douglas R. Adkins, MD, professor and medical oncologist in the John T. Milliken Department of Medicine of Washington University in St. Louis, MO, spoke with CancerNetwork® about next steps for researching pembrolizumab (Keytruda)-based treatment in patients with head and neck squamous cell carcinoma (HNSCC). The discussion was contextualized by findings from the phase 3 KEYNOTE-689 (NCT03765918) trialassessing the addition of neoadjuvant and adjuvant pembrolizumab to standard-of-care (SOC) surgery and radiation or chemoradiotherapy in this patient population he presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

Adkins suggested that data from the trial provide a new foundation to develop strategies that can elicit higher cure rates among patients with locally advanced head and neck cancer, given the potential of relapse even with the addition of neoadjuvant and adjuvant pembrolizumab to surgery followed by radiation or chemoradiation. He explained that potential strategies may include adding other therapeutic agents to pembrolizumab to enhance its efficacy.

Another opportunity, he claims, might include an investigation into the relative contribution of pembrolizumab to responses both before and after surgery in this patient population. He concluded by emphasizing the potential to develop new research pathways that expand upon the results uncovered in the investigation of KEYNOTE-689.

Transcript

[The KEYNOTE-689 data] provide a new foundation to work on developing alternative or additional strategies that can further improve the chance of curing patients with locally advanced head and neck cancer. Relapse is still an event that does occur in patients who are treated with pembrolizumab, along with surgery-based treatment. There are opportunities to further reduce the chance of relapse and improve the [cure rates].

These opportunities could include [adding] drugs to pembrolizumab before and after surgery-based treatment––drugs that might enhance the efficacy of pembrolizumab. There are other opportunities to investigate the relative contribution of pembrolizumab given before surgery vs given after surgery. There are rich opportunities to develop new research pathways that build upon the results of the perioperative pembrolizumab approach that was investigated in KEYNOTE-689.

Reference

Adkins D, Haddad RI, Tao Y, et al. Neoadjuvant and adjuvant pembrolizumab plus standard of care (SOC) in resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC): exploratory efficacy analyses of the phase 3 KEYNOTE-689 study. J Clin Oncol. 2025;43(suppl 16):6012. doi:10.1200/JCO.2025.43.16_suppl.6012