175PLevels of circulating fibroblast growth factor (FGF) 23 and prognosis of cancer patients with bone metastasis

Background: The FGF signaling network plays a key role in tumorigenesis and is recognized as a potential therapeutic target. FGF23 is predominately expressed in bone osteocytes and can act as an autocrine, paracrine and/or endocrine growth factor in cancer. In this study, we aimed to assess the role of circulating FGF23 levels in the prognosis of cancer patients with bone metastases. Methods: This study included a cohort of 112 patients with cancer (63% breast;16% prostate) and metastatic bone disease treated with bone targeting agents (BTA), in which serum baseline FGF23 was quantified by ELISA and further dichotomized in two groups (FGF23high and FGF23low). Cut-off was defined by mean + one standard deviation. The association of FGF23 with overall survival (OS) and with time to skeletal related events (TTSRE) was investigated. Time to event outcomes was calculated using the Kaplan-Meier method and tested using univariate/multivariate Cox regression models controlling for established prognostic factors across patients with solid tumors and bone metastases: extra-bone involvement, urinary N-terminal telopeptide (uNTX), presence of bone fractures, and calcemia. Results: Mean FGF23 was 38.16 ± 26.15 pg/mL (interquartile range [IQR] 19.77-50.72). 16.8% of patients were classified as FGF23high (n = 19). Baseline characteristics were balanced between groups, except for the median uNTX level, which was higher in the FGF23high group (824.30 vs 118.02 nmol BCE/mmol creatinine, p = 0.040). Median time from beginning of BTA was similar between groups (1.28 vs 1.10 months, p = 0.161). After a median follow-up of 26.0 months (IQR 13.0-47.0), median OS was 34.4 months in the FGF23low group and 12.2 months in the FGF23high group (multivariate HR 0.18, 95% CI 0.07 – 0.44, p = 0.001; univariate p = 0.001). As a continuous variable, FGF23 at baseline kept its prognostic association (p = 0.001). Patients with FGF23low status at baseline had a longer TTSRE (13.0 vs 2.0 months, p = 0.04). Conclusions: In this exploratory cohort, patients in the FGF23low group had a longer OS and TTSRE. Further studies are warranted to define its role as a prognostic biomarker and as a potential predictor of response to drugs targeting the FGF axis. Editorial acknowledgement: Joana Cavaco Silva - Medical Writer (Medical Oncology Department - Hospital de Santa Maria - Centro Hospitalar Lisboa Norte). Legal entity responsible for the study: Instituto de Medicina Molecular. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.