847P The prognostic value of chemosensitivity, estimated by the modeled CA-125 KELIM, in ovarian cancer patients treated with neo-adjuvant chemotherapy in the Netherlands

Abstract

Chemosensitivity and completeness of cytoreductive surgery (IDS) are important prognostic factors in advanced stage epithelial ovarian cancer (EOC). Robust chemosensitivity markers are required to tailor treatment. This study aims to validate the prognostic value of the CA-125 ELIMination rate constant K (KELIM), as an early chemosensitivity marker, during neoadjuvant chemotherapy (NACT) in a population-based cohort. Patients diagnosed with advanced stage (FIGO IIb-IV) EOC between 2008-2015 were identified from the Netherlands Cancer Registry. Patients treated with NACT with >2 CA-125 measurements were included. CA-125 profiles were fit with a nonlinear mixed-effect model to calculate KELIM (with favorable KELIM >0.06 days-1). The predictive value of KELIM regarding completeness of IDS; progression-free survival (PFS); overall survival (OS); progression free survivorship (PS)(PFS > 5 years) were assessed using univariate and multivariate analyses. 1582 patients were included. In multivariable logistic regression, higher std KELIM was prognostic for a higher likelihood of complete IDS (OR=5.25, 95% 3.68-7.59). In multivariable cox regression, OS was significantly associated with a favorable KELIM (HR = 0.75, 95%CI 0.65-0.87), high-risk disease (FIGO IV or III + incomplete IDS) (HR = 1.63, 95%CI 1.40-1.89) and tumor response rate (complete(CR) or partial remission(PR) after treatment)(HR = 0.41, 95%CI 0.33-0.50). PFS was associated with a favorable KELIM (HR = 0.77, 95%CI 0.67-0.89), high-risk disease (HR = 1.67, 95%CI 1.44-1.94) and tumor response rate (CR/PR)(HR 0.35, 95%CI 0.28-0.43). 2.2% of patients were progression-free survivors. In multivariable logistic regression high-risk disease (OR=0.19, 95% CI 0.08-0.42) and std KELIM (OR=4.17, 95% CI 1.61-10.64) were prognostic for PS. Patients with FIGO IV and a favorable KELIM had no survival benefit in case of incomplete IDS compared to no IDS at all. This large population-based cohort confirms that KELIM during NACT exhibits an independent prognostic value for completeness of IDS, PFS, OS and progression free survivorship.