Perioperative pembrolizumab demonstrates clinical benefit in locally advanced HNSCC

Immune-checkpoint inhibitors (ICIs) have been established as a key component of therapy for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, most patients with HNSCC present with locally advanced disease, and initial efforts to integrate ICIs concurrent with or following curative-intent local treatment have produced disappointing results. Now, data from the phase III KEYNOTE-689 trial indicate that a perioperative approach improves outcomes in this setting.

In KEYNOTE-689, 714 patients with newly diagnosed, resectable stage III–IVA HNSCC (laryngeal, hypopharyngeal, oropharyngeal or in the oral cavity) were randomly assigned (1:1) to undergo standard surgery and adjuvant (chemo)radiotherapy with versus without 2 neoadjuvant and 15 adjuvant cycles of pembrolizumab. The primary end point was event-free survival (EFS) sequentially assessed in the PD-L1 combined positive score (CPS) ≥10 subgroup (n = 465; 65.1%), the PD-L1 CPS ≥1 subgroup (n = 682; 95.5%), and then in the entire cohort.