ACE and CXCL10 as predictive biomarkers in the LEA study

Haba, J. de la ; Aguilar, E. Aranda ; Morales, S. ; García-Sáenz, J.A. ; Guerrero, A. ; Martínez, N. ; Antón, A. (Universidad de Zaragoza) ; Muñoz, M. ; Ramos, M. ; Gil-Gil, M. ; Margelí, M. ; Servitja, S. ; Bermejo, B. ; Cruz, J. ; Lescure, A. Rodríguez ; Casas, M. ; Sánchez-Aragó, M. ; Caballero, R. ; Carrasco, E. ; Martin, M.

Resumen: Background: LEA Study (GEICAM/2006-11/GBG51), is a randomized clinical trial comparing bevacizumab in combination with endocrine therapy (ET + B) with endocrine therapy (ET) in postmenopausal women with advanced or metastatic HR-positive/HER2-negative breast cancer (BC) with indication of hormonotherapy as first-line treatment. Patients with secondary hypertension had better progression-free survival (PFS) and overall survival (OS). We have evaluated the role of two hypertension-related biomarkers, Angiotensin-Converting Enzyme (ACE) and Small-Inducible Cytokine B10 (CXCL10) as prognostic and/or predictive biomarkers of benefit to bevacizumab in the first line metastatic disease.
Methods: From 380 patients, 266 were included in 33 Spanish sites. Median age was 64 years, 63.5% had measurable disease, 97.4% were metastatic at randomization, 51.5% had visceral disease and 52.6% received previous chemotherapy. PFS was 14.3 months (range 0.8-61.1), OS was 34 months (range 0.8-71.6) and 93 patients had Objective Response (OR). We analyzed 124 plasma samples collected before treatment (52 from ET and 72 from ET + B arms). Circulating levels of ACE and CXCL10 were determined by ELISA. ACE levels of 115ng/ml and 135ng/ml were pre-defined as cutoff values. CXCL10 was explored as a quantitative variable.
Results: PFS was 15.1 months (range 1.4-61.1), OS was 31.1 months (range 2.8-61.1) and 40.3% had OR. OR was significantly different between treatment arms (p < 0.001) but not PFS or OS. Median ACE concentration was 130.9ng/ml (range 35.3-315.4). Low ACE (<135ng/ml) had better PFS in the whole population (p = 0.048) and in the ET + B arm (p = 0.041). ACE cutoff of 115 ng/ml was not able to identify any subgroup with better prognosis. Median CXCL10 concentration was 230.3pg/ml (range 15.1-4129.6). A higher expression of CXCL10 was significantly associated with worse OS in the whole population (p < 0.0001) and each treatment arm (p = 0.002 and p = 0.001 in ET and ET + B, respectively). No association with OR were identified neither for ACE nor for CXCL10.
Conclusions: ACE levels could be considered a prognostic and a bevacizumab predictive biomarker of PFS. CXCL10 could be prognostic of OS. Confirmatory studies are warranted.

Idioma: Inglés

DOI: 10.1093/annonc/mdw363.83

Año: 2016

Publicado en: ANNALS OF ONCOLOGY 27, Suppl. 6 (2016), [135P] vi41
ISSN: 0923-7534

Factor impacto JCR: 11.855 (2016)

Categ. JCR: ONCOLOGY rank: 10 / 217 = 0.046 (2016) - Q1 - T1

Factor impacto SCIMAGO: 5.096 - Hematology (Q1) - Oncology (Q1) - Medicine (miscellaneous) (Q1)

Tipo y forma: Comunicación congreso (Versión definitiva)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)