PURPOSE: Patients with recurrent or metastatic sinonasal squamous cell carcinoma (R/M SNSCC) lack standardized systemic treatment and prospective studies. We evaluated the anti-tumor response and safety of pembrolizumab with nab-paclitaxel and platinum in R/M SNSCC. PATIENTS AND METHODS: R/M SNSCC patients received pembrolizumab 200mg, nab-paclitaxel 260mg/m2 plus cisplatin 75 mg/m2 or carboplatin at an area under the curve 5 on day 1 every 21 days for up to six cycles, followed by pembrolizumab maintenance until progression or unacceptable toxicity or 35 cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Immunohistochemistry and high-resolution sequencing of the tumor samples were performed. RESULTS: The ORR in 20 patients was 60.0% (95% CI: 36.1%-80.9%) and two patients (2/20, 10%) achieved CR. The DCR was 100%. Median follow-up was 18.1 months (range:5.2-31.7), the median PFS was 12.2 months (95% CI: 9.0 months-not estimated) and the median OS was not reached. Patients with PD-L1 CPS ≥20 exhibited better ORR (80.0% vs 28.6%, p=0.144), median PFS (not reached vs 7.0 months, p=0.0137), and median OS (not reached vs 17.8 months, p=0.0401) compared to those with PD-L1 CPS <
20. Grade 3/4 treatment-related adverse events (AE) accounted for 30.0% (6/20), and all come from hematologic toxicity. Hypothyroidism was the most common immune-related AE (12/20, 60.0%). CONCLUSIONS: Pembrolizumab plus nab-paclitaxel and platinum shows promising antitumor activity and manageable safety in first-line R/M SNSCC patients.