Pembrolizumab with Chemotherapy for Patients with Recurrent or Metastatic Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma: A Prospective Phase ll Study.

PURPOSE: Patients with recurrent or metastatic sinonasal squamous cell carcinoma (R/M SNSCC) lack standardized systemic treatment and prospective studies. We evaluated the antitumor response and safety of pembrolizumab with nab-paclitaxel and platinum in R/M SNSCC.

PATIENTS AND METHODS: Patients with R/M SNSCC received pembrolizumab 200 mg and nab-paclitaxel 260 mg/m2 plus cisplatin 75 mg/m2 or carboplatin at an AUC 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 the objective response rate (ORR). Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), and safety. IHC and high-resolution sequencing of the tumor samples were performed.

RESULTS: The ORR in 20 patients was 60.0% (95% confidence interval, 36.1%-80.9%), and two patients (2/20, 10%) achieved complete response. The disease control rate was 100%. The median follow-up was 18.1 months (range, 5.2-31.7), the median PFS was 12.2 months (95% confidence interval, 9.0 months-not estimated), and the median OS was not reached. Patients with a PD-L1 combined positive score ≥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 with those with a PD-L1 combined positive score <20. Grade 3/4 treatment-related adverse events (AE) accounted for 30.0% (6/20) of AEs, and all were hematologic toxicities. 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 patients with first-line R/M SNSCC.