Multidimensional biomarker predicts disease control in response to immunotherapy in recurrent or metastatic head and neck squamous-cell carcinoma.

Autor: Flanagan KC; Cofactor Genomics, Inc., 4044 Clayton Ave, St. Louis, MO, 63110, USA. kevin_flanagan@cofactorgenomics.com., Earls J; Cofactor Genomics, Inc., 4044 Clayton Ave, St. Louis, MO, 63110, USA., Schillebeeckx I; Cofactor Genomics, Inc., 4044 Clayton Ave, St. Louis, MO, 63110, USA., Hiken J; Cofactor Genomics, Inc., 4044 Clayton Ave, St. Louis, MO, 63110, USA., Wellinghoff RL; Cofactor Genomics, Inc., 4044 Clayton Ave, St. Louis, MO, 63110, USA., LaFranzo NA; Cofactor Genomics, Inc., 4044 Clayton Ave, St. Louis, MO, 63110, USA., Bradley ZS; Cofactor Genomics, Inc., 4044 Clayton Ave, St. Louis, MO, 63110, USA., Babbitt J; Cofactor Genomics, Inc., 4044 Clayton Ave, St. Louis, MO, 63110, USA., Westra WH; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Hsu R; Vision Radiology, Dallas, TX, USA., Nadauld L; Intermountain Healthcare, St. George, UT, USA., Mcleod H; Intermountain Healthcare, St. George, UT, USA., Firth SD; Intermountain Healthcare, St. George, UT, USA., Sharp B; Intermountain Healthcare, St. George, UT, USA., Fuller J; Intermountain Healthcare, St. George, UT, USA., Vavinskaya V; Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA., Sutton L; Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA., Deichaite I; Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA., Bailey SD; Appalachian Regional Healthcare, Hazard, KY, USA., Sandulache VC; Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA., Rendo MJ; Hematology and Oncology, Brooke Army Medical Center, San Antonio, TX, USA., Macdonald OK; Cancer Care Northwest, Spokane Valley, WA, USA., Welaya K; CoxHealth Medical Oncology, Springfield, MO, USA., Wade JL 3rd; Decatur Memorial Hospital, Decatur, IL, USA., Pippas AW; John B Amos Cancer Center, Columbus Regional Research Institute, Centricity Research, Columbus, GA, USA., Slim J; Multicare Institute for Research and Innovation, Tacoma, WA, USA., Bank B; Northwest Oncology and Hematology, Elk Grove Village, IL, USA., Saccaro SJ; Ochsner Lafayette General Medical Center, Lafayette, LA, USA., Sui X; Providence Regional Cancer System, Lacey, WA, USA., Akhtar A; Revive Research Institute, Sterling Heights, MI, USA., Balaraman S; Revive Research Institute, Sterling Heights, MI, USA., Kossman SE; Sharp Clinical Oncology Research, San Diego, CA, USA., Sonnier SA; Touro Infirmary, New Orleans, LA, USA., Shenkenberg TD; Valley Cancer Associates, Harlingen, TX, USA., Alexander WL; William Beaumont Army Medical Center and The Geneva Foundation, Fort Bliss, TX, USA., Price KA; Mayo Clinic, Rochester, MN, USA., Bane CL; Dayton Physicians Network/Precision Cancer Research, Dayton, OH, USA., Ley J; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Messina DN; Cofactor Genomics, Inc., 4044 Clayton Ave, St. Louis, MO, 63110, USA., Glasscock JI; Cofactor Genomics, Inc., 4044 Clayton Ave, St. Louis, MO, 63110, USA., Cohen EEW; Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA., Adkins DR; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Duncavage EJ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Jazyk: angličtina
Zdroj: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2023 Nov; Vol. 149 (15), pp. 14125-14136. Date of Electronic Publication: 2023 Aug 08.
DOI: 10.1007/s00432-023-05205-z
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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