High serum level of C-reactive protein is associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib
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Erlotinib is a low molecular weight tyrosine kinase inhibitor (TKI) directed at epidermal growth factor receptor (EGFR), widely used in the treatment of locally advanced or metastatic-stage non-small cell lung cancer (NSCLC). Although introduction of EGFR-TKIs have significantly extended survival of advanced-stage NSCLC patients, their efficacy in the entire patient population is relatively low. Aside from activating EGFR mutations, no reliable biochemical or molecular predictors of response to erlotinib have been established. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in patients with advanced-stage NSCLC treated with erlotinib. We retrospectively analyzed clinical data of 595 patients with advanced-stage NSCLC (IIIB or IV) treated with erlotinib. Serum CRP was measured using an immunoturbidimetric method. High baseline levels of CRP (≥10 mg/l) were measured in 387 (65 %) patients, and normal levels (<10 mg/l) were measured in 208 (35 %) patients. The median progression-free survival (PFS) and overall survival (OS) for patients with high CRP was 1.8 and 7.7 compared to 2.8 and 14.4 months for patients with low CRP (p < 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that CRP was significantly associated with PFS and also with OS (hazard ratio (HR) = 1.57, p < 0.001, and HR = 1.63, p < 0.001, respectively). In conclusion, the results of the conducted retrospective study suggest that high baseline level of CRP was independently associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib. CRP is a commonly used biomarker which is simple and easy to detect, and thus, it is feasible for the use in the routine clinical practice.
KeywordsC-reactive protein Lung cancer NSCLC EGFR-TKI Erlotinib Prediction Biomarker
The authors would like to thank all the patients who voluntarily took part in the observational, population-based registry TULUNG. This study is supported by the Ministry of Health, Czech Republic [conceptual development of research organizations: Faculty Hospital in Pilsen - FNPl (00669806) and Masaryk Memorial Cancer Institute - MMCI (00209805)] and by the project CZ.1.05/2.1.00/03.0076 from European Regional Development Fund.
Conflicts of interest
JF has received honoraria from AstraZeneca, Roche and Novartis for consultations and lectures unrelated to this project. TB has received honoraria from Roche for consultations and lectures unrelated to this project. AP has received honoraria from GSK, Roche and Bayer for consultations and lectures unrelated to this project. OF, MP, OT, MM, LB, JR and ZB declare that they have no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence this work.
- 5.Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, et al. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012;13:300–8.CrossRefPubMedGoogle Scholar
- 6.Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12:735–42.CrossRefPubMedGoogle Scholar
- 7.Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–46.CrossRefPubMedGoogle Scholar
- 12.Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumours. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.CrossRefGoogle Scholar
- 17.Egenhofer C, Alsdorff K, Fehsel K, Kolb-Bachofen V. Membrane associated C-reactive protein on rat liver macrophages is synthesized within the macrophages, expressed as neo-C-reactive protein and bound through a C-reactive protein-specific membrane receptor. Hepatology. 1995;18:1216–23.Google Scholar