Predictive biomarkers for patients with head and neck squamous cell carcinoma (HNSCC) treated with immune check point inhibitors (ICIs).

Abstract

e18000 Background: HNSCC patients present challenges for clinicians, especially in recurrent/metastatic (R/M) cases. ICIs show promise survival outcome but require predictive biomarkers to identify responsive patients. In Keynote-048, pembrolizumab improved overall survival (OS) in PD-L1 expression with combined positive score (CPS) ≥ 1. Other studies have explored biomarkers such as the neutrophil-to-lymphocyte ratio and pan-immune-inflammation value (PIV), which have shown associations with clinical outcomes; however, response rates were not reported. This study aims to identify clinical factors that can better predict which patients will benefit from ICI therapy. Methods: This retrospective study was conducted at three medical centers in Taiwan. Eligible patients included those with histologically confirmed HNSCC and R/M disease who received ICI therapy. The study endpoints consisted of the overall response rate (ORR) and OS. The ORR was evaluated by the RECIST rules. Prognostic factors for OS were analyzed using univariate analysis followed by multivariate Cox proportional hazards analysis. Clinical response to ICI therapy was categorized as good response (CR/PR) and not good response (SD/PD). Univariate and binary logistic regression analyses were performed to determine the association of the variables with good response, and the association was evaluated by odds ratio (OR). All statistical tests were considered significant at a p-value < 0.05, and analyses were performed using SAS version 9.4. Results: A total of 318 patients were enrolled from January 2017 to September 2023, with a median follow-up of 473 days. Among them, 60% received ICI-based second-line treatment, while 40% underwent first-line treatment. In univariate analyses, not good response of ICI therapy was associated with M1 stage, cisplatin intervals < 6 months, cetuximab before ICI therapy and high PIV. The primary tumor location of oropharynx is related to good response. In multivariable analysis, the probability of having no response increased with M1 stage, cetuximab before ICI therapy and high PIV. The primary tumor location of oropharynx is related to good response. For OS, univariate analyses indicated that shortened OS was linked to M1 stage, prior cetuximab therapy, CPS < 1, high PIV, and poor clinical response to ICI. The primary tumor location in the oropharynx was associated with prolonged OS. In multivariable analysis, CPS < 1, high PIV, and poor clinical response to ICI were identified as independent unfavorable prognostic factors for OS. Conclusions: In conclusion, our findings demonstrate that M1 disease, prior cetuximab therapy, and high PIV are independently associated with poorer responses to ICI therapy. Additionally, CPS < 1, high PIV, and suboptimal clinical responses to ICI therapy have a significant negative impact on prognosis.