Monotherapy With Immune Checkpoint Inhibitors in Patients With Recurrent and/or Metastatic Sinonasal Squamous Cell Carcinoma

ABSTRACT Introduction Sinonasal squamous cell carcinoma (SNSCC) is a rare malignancy with limited data on effective treatment modalities in the recurrent and/or metastatic (r/m) setting. While immune checkpoint inhibitors (ICIs) have shown promise in treating head and neck cancers, in general, their effects in SNSCC remain poorly understood. Furthermore, SNSCC patients are frequently excluded from clinical trials, limiting the evidence base for ICI efficacy in this specific subgroup. Therefore, our study evaluated the efficacy and safety of single‐agent ICI therapy in r/m SNSCC. Methods We conducted a retrospective multicenter analysis of all r/m SNSCC patients treated with single‐agent ICIs from July 2018 to December 2023 at two tertiary reference centers. Results A total of 18 patients received either Pembrolizumab ( n = 8) or Nivolumab ( n = 10) for r/m SNSCC. The overall response rate (ORR) to immunotherapy was 11.1% (2/18), with a disease control rate (DCR) of 27.8% (5/18) and a mean PFS and OS of 11.7 (95% CI: 2.3–21.0) months and 18.9 (95% CI: 8.3–29.5) months respectively. Two (11.1%) immune‐related adverse events led to treatment discontinuation. Univariable analysis revealed high pathological grading ( p = 0.049) as a negative prognostic factor for PFS. In an exploratory comparison with a larger cohort of 121 patients with r/m SCC of the larynx, oropharynx, hypopharynx, or oral cavity receiving ICI therapy, outcomes in SNSCC appeared broadly similar, with no statistically significant differences in PFS ( p = 0.153), OS ( p = 0.152), ORR ( p = 0.401), or DCR ( p = 0.359). Conclusion Immunotherapy may represent a treatment option for patients with SNSCC. Given the limited sample size, these results should be interpreted with caution. Our findings highlight the urgent need to include SNSCC patients in future prospective trials to clarify the role of immunotherapy in this underrepresented population.