Early on-treatment C-reactive protein and its kinetics predict survival and response in recurrent and/or metastatic head and neck cancer patients receiving first-line pembrolizumab

Markus Haas; Alexander Lein; Thorsten Fuereder; Julia Schnoell; Faris F Brkic; David T Liu; Lorenz Kadletz-Wanke; Gregor Heiduschka; Bernhard J Jank

doi:10.1007/s10637-023-01388-x

Early on-treatment C-reactive protein and its kinetics predict survival and response in recurrent and/or metastatic head and neck cancer patients receiving first-line pembrolizumab

Invest New Drugs. 2023 Oct;41(5):727-736. doi: 10.1007/s10637-023-01388-x. Epub 2023 Aug 21.

Authors

Markus Haas¹, Alexander Lein¹, Thorsten Fuereder², Julia Schnoell¹, Faris F Brkic¹, David T Liu¹, Lorenz Kadletz-Wanke¹, Gregor Heiduschka³, Bernhard J Jank¹

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria.
² Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria.
³ Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria. gregor.heiduschka@meduniwien.ac.at.

Abstract

Purpose: First-line immune checkpoint blockade has improved the prognosis of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), but response rates remain low. In this study, we aimed to investigate the prognostic value of CRP and its early kinetics to predict response and survival in R/M HNSCC.

Methods: A total of 87 patients who received first-line pembrolizumab for R/M HNSCC were analyzed. Three-fold cross-validation was used to estimate cut-off points of CRP at baseline and on-treatment (day 40 ± 10). Treatment response and survival were analyzed according to early CRP kinetics. The neutrophil-to-lymphocyte ratio (NLR) was used as a benchmark for the prognostic performance of CRP.

Results: On-treatment CRP below 2 mg/dl, 4x the upper limit of normal (ULN), was associated with increased overall survival (OS), while on-treatment CRP below 3 mg/dl (6x ULN) was correlated with a higher disease control rate (DCR) and increased progression-free survival (PFS). CRP flare-responders and CRP responders showed a higher DCR and longer PFS than CRP non-responders. An NLR above 6 was a negative prognosticator for progression. In multivariable analysis, on-treatment CRP prevailed as the only significant prognosticator for OS (HR: 4.97, CI95%: 2.18-11.32, p < 0.001) and PFS (HR: 2.07, CI95%: 1.07-3.99, p = 0.030).

Conclusion: On-treatment CRP was identified as a prognostic biomarker for objective response and survival in R/M HNSCC patients receiving first-line pembrolizumab and could be easily incorporated into clinical practice as a widely available and cost-effective biomarker.

Keywords: Biomarkers; C-Reactive protein; Head and Neck Neoplasms; Immunotherapy; Kinetics.