Multidimensional biomarker predicts disease control in response to immunotherapy in recurrent or metastatic head and neck squamous-cell carcinoma.
Journal of cancer research and clinical oncology
Biomarker; HNSCC; Immune checkpoint inhibitors; PD-1; PD-L1; Pembrolizumab
PURPOSE: Anti-PD-1 therapy provides clinical benefit in 40-50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity.
METHODS: Clinical treatment and outcomes data for 103 RM-HNSCC patients were paired with RNA-sequencing data from formalin-fixed patient samples. Using logistic regression methods, we developed a novel biomarker classifier based on expression patterns in the tumor immune microenvironment to predict disease control with monotherapy PD-1 inhibitors (pembrolizumab and nivolumab). The performance of the biomarker was internally validated using out-of-bag methods.
RESULTS: The biomarker significantly predicted disease control (65% in predicted non-progressors vs. 17% in predicted progressors, p < 0.001) and was significantly correlated with overall survival (OS; p = 0.004). In addition, the biomarker outperformed PD-L1 IHC across numerous metrics including sensitivity (0.79 vs 0.64, respectively; p = 0.005) and specificity (0.70 vs 0.61, respectively; p = 0.009).
CONCLUSION: This novel assay uses tumor immune microenvironment expression data to predict disease control and OS with high sensitivity and specificity in patients with RM-HNSCC treated with anti-PD-1 monotherapy.
Flanagan, Kevin C; Earls, Jon; Schillebeeckx, Ian; Hiken, Jeffrey; Wellinghoff, Rachel L; LaFranzo, Natalie A; Bradley, Zachary S; Babbitt, Joey; Westra, William H; Hsu, Raymond; Nadauld, Lincoln; Mcleod, Howard; Firth, Sean D; Sharp, Brittany; Fuller, Josh; Vavinskaya, Vera; Sutton, Leisa; Deichaite, Ida; Bailey, Samuel D; Sandulache, Vlad C; Rendo, Matthew J; Macdonald, Orlan K; Welaya, Karim; Wade, James L; Pippas, Andrew W; Slim, Jennifer; Bank, Bruce; Saccaro, Steven J; Sui, Xingwei; Akhtar, Adil; Balaraman, Savitha; Kossman, Steven E; Sonnier, Scott A; Shenkenberg, Todd D; Alexander, Warren L; Price, Katherine A; Bane, Charles L; Ley, Jessica; Messina, David N; Glasscock, Jarret I; Cohen, Ezra E W; Adkins, Douglas R; and Duncavage, Eric J, "Multidimensional biomarker predicts disease control in response to immunotherapy in recurrent or metastatic head and neck squamous-cell carcinoma." (2023). Articles, Abstracts, and Reports. 7765.