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Pembrolizumab improved survival in recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC) patients. The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.
Neoadjuvant pembrolizumab (200 mg) was administered and followed 2–3 weeks later by surgical tumor ablation. Post-operative (chemo) radiation was planned. High-risk pathology patients (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (<10%), pTR-1 (10–49%), and pTR-2 (≥50%). Co-primary endpoints were pTR-2 among all patients and one-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated ( ClinicalTrials.gov NCT02296684).
Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3–4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among eighteen patients with high-risk pathology was 16.7% (95%CI: 3.6–41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFN-γ activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0, and confirmed clonal loss in some patients.