Addition of Pembrolizumab to SOC May Enhance HNSCC Cure Rates

In a conversation with CancerNetwork®, Douglas R. Adkins, MD, discussed what the standards of care (SOCs) were for patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC). The discussion served as context for findings from the phase 3 KEYNOTE-689 (NCT03765918) trial assessing the addition of neoadjuvant and adjuvant pembrolizumab (Keytruda) to SOC in this patient population he presented at the 2025 American Society of Clinical Oncology Annual Meeting.1

Adkins is a professor and medical oncologist in the John T. Milliken Department of Medicine of Washington University in St Louis, Missouri.

He began by contextualizing the state of head and neck cancer in the US, explaining that of the approximately 60,000 new cases every year, most patients have locally advanced disease. He remarked that the SOC for this patient group was surgery followed by radiation or chemoradiation, iterating that the cure rate for this SOC option was less than 50%.

Furthermore, he expressed that the addition of pembrolizumab to this regimen, both before and after surgery, was thought to help enhance cure rates for this patient group. He concluded by affirming that the trial supported the hypothesis, given a significantly improved major pathological response (mPR) rate, as well as event-free survival (EFS) and distant metastasis-free survival.

Results from the trial revealed that pembrolizumab extended EFS by more than 20 months, with the investigational arm (n = 363) experiencing a median EFS of 51.8 months (95% CI, 37.5-not reached [NR]) vs 30.4 months (95% CI, 21.8-50.1) with SOC alone (n = 351; HR, 0.73; 95% CI, 0.58-0.92; P = .0041). Furthermore, among patients in the respective arms, the mPRs were 9.4% and 0%, with an estimated difference of 9.3% (95% CI, 6.7%-12.8%; P < .00001).

Transcript:

For context, in the US, each year, about 60,000 new cases of head and neck cancer [occur]. Of these cases, most patients have locally advanced disease and are therefore candidates for [the current SOC for] curative therapy, typically with surgery followed by radiation with or without chemotherapy…. The chance of curing patients with the current SOC is just under 50%; there lies the problem.

[Many] patients unfortunately develop recurrence of their cancer after [SOC]. The introduction of pembrolizumab before and after surgery [with] radiation offers the opportunity to improve the chance of [curing them]. Indeed, that is what the KEYNOTE-689 trial showed.

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