Prognostic importance of cell-free DNA in chemotherapy resistant ovarian cancer treated with bevacizumab

• Published in: European journal of cancer (1990) Vol. 50; no. 15; pp. 2611 - 2618
• Main Authors: Steffensen, Karina Dahl, Madsen, Christine Vestergaard, Andersen, Rikke Fredslund, Waldstrøm, Marianne, Adimi, Parvin, Jakobsen, Anders
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.10.2014; Elsevier
• Subjects: Adult; Aged; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - therapeutic use; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Bevacizumab; Biological and medical sciences; cfDNA; DNA, Neoplasm - blood; DNA, Neoplasm - genetics; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Hematology, Oncology and Palliative Medicine; Humans; Hypertension - chemically induced; Kaplan-Meier Estimate; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Multiresistant; Multivariate Analysis; Neoplasms, Glandular and Epithelial - blood; Neoplasms, Glandular and Epithelial - drug therapy; Ovarian cancer; Ovarian Neoplasms - blood; Ovarian Neoplasms - drug therapy; Pharmacology. Drug treatments; Prognosis; Proteinuria - chemically induced; Real-Time Polymerase Chain Reaction; Treatment Outcome; Tumors; Multiresistant; Prognosis; cfDNA; Bevacizumab; Ovarian cancer; Antineoplastic agent; Ovary cancer; Monoclonal antibody; Malignant tumor; Female genital diseases; Immunomodulator; Ovarian diseases; Chemotherapy; Treatment; Cancerology; Vascular endothelium growth factor; DNA; Multiple resistance; Antiangiogenic agent; Cell free system; Cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2014.06.022

Abstract Aim Treatment of multiresistant epithelial ovarian cancer (EOC) is palliative and patients who have become resistant after multiple lines of chemotherapy often have an unmet need for further and less toxic treatment. Anti-angiogenic therapy has attracted considerable attention in the treatment of EOC in combination with chemotherapy. However, only a minor subgroup will benefit from the treatment and there is an obvious need for new markers to select such patients. The purpose of this study was to investigate the effect of single-agent bevacizumab in multiresistant EOC and the importance of circulating cell-free DNA (cfDNA) in predicting treatment response. Methods One hundred and forty-four patients with multi-resistant EOC were treated with single-agent bevacizumab 10 mg/kg every three weeks. Baseline plasma samples were analysed for levels of cfDNA by real-time polymerase chain reaction (PCR). Results Eighteen percent responded to treatment according to CA125 and 5.6% had partial response by Response Evaluation Criteria in Solid Tumours (RECIST). Stable disease was seen in 53.5% and 48.6% of the patients by CA125 and RECIST, respectively. Median progression free survival (PFS) and overall survival (OS) were 4.2 and 6.7 months, respectively. Cell-free DNA was highly correlated to PFS ( p = 0.0004) and OS ( p = 0.005) in both univariate and multivariate analyses (PFS, hazard ratio (HR) = 1.98, p = 0.002; OS, HR = 1.66, p = 0.02), as patients with high cfDNA had a poor outcome. Conclusions Single-agent bevacizumab treatment in multiresistant EOC appears to be a valuable treatment option with acceptable side-effects. Cell-free DNA showed independent prognostic importance in patients treated with bevacizumab and could be applied as an adjunct for treatment selection.