Pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic nasal cavity and paranasal sinus squamous-cell carcinoma: A prospective phase ll study.

6022 Background: Patients with recurrent or metastatic sinonasal squamous-cell carcinoma (R/M SNSCC) lack standardized systemic treatment protocols and prospective studies. While pembrolizumab with platinum and fluorouracil is established as first-line treatment for R/M head and neck squamous-cell carcinoma, and its combination with carboplatin and paclitaxel shows promise, we evaluated the efficacy and safety of pembrolizumab with nab-paclitaxel and platinum in R/M SNSCC. Methods: This is a single-arm phase 2 study, patients with R/M SNSCC received pembrolizumab 200mg, nab-paclitaxel 260mg/m 2 plus cisplatin 75 mg/m 2 or carboplatin AUC5 on day 1 every 21 days for up to six cycles followed by pembrolizumab maintenance therapy until progression or unacceptable toxicity or 35 cycles, whichever occurred first. 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: From 10 March 2022 to 31 October 2024, 20 patients were enrolled. The ORR was 60% (95%CI: 0.36-0.81) and two patients (2/20, 10%) achieved CR. The DCR was 100%. Median follow-up was 18.05 months(range:5.2-31.7), with a median PFS of 12.2 months (95%CI: 9 months-not estimated) and an unreached median OS. Patients with PD-L1 CPS ≥20 exhibited better ORR (80% vs 28.6%, p=0.144), median PFS (not reached vs 7 months, p=0.0137), and median OS (not reached vs 17.8 months, p=0.0401) compared to those with PD-L1 CPS < 20. ORR was 50% (2/4) in HPV-positive patients and 53.8% (7/13) in HPV-negative patients. The most common genetic alterations were TP53, EGFR, CDKN2A mutations and amplifications in the 11q13 region (including CCND1, FGF19, FGF4, and FGF3 genes). Median TMB was 4 mut/Mb (range 2-13), with no significant difference observed between responders and non-responders. Grade 3/4 Treatment-Related Adverse Events (TRAEs) only accounted for 30% (6/20), and all come from hematologic toxicity. Hypothyroidism was the most common irAEs (12/20, 60%). Conclusions: Pembrolizumab plus nab-paclitaxel and platinum shows promising antitumor activity and manageable safety in first-line R/M SNSCC patients. Clinical trial information: ChiCTR2200057343 .