Vincenza Conteduca1, Elena Castro2, Daniel Wetterskog3, Emanuela Scarpi4, Anuradha Jayaram3, Nuria Romero-Laorden5, David Olmos6, Giorgia Gurioli4, Cristian Lolli4, Maria Isabel Sáez7, Javier Puente8, Giuseppe Schepisi4, Samanta Salvi4, Anna Wingate3, Ana Medina9, Rosa Querol-Niñerola10, Mercedes Marin-Aguilera11, Jose Angel Arranz12, Giuseppe Fornarini13, Umberto Basso14, Begoña Mellado11, Enrique Gonzalez-Billalabeitia15, Gerhardt Attard16, Ugo De Giorgi4. 1. Istituto Scientifico Romagnolo per Io Studio e La Cura dei Tumori (IRST) IRCCS, Meldola, Italy; University College London Cancer Institute, London, UK. Electronic address: vincenza.conteduca@irst.emr.it. 2. Prostate Cancer Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Hospital Universitario Quirón, Madrid, Spain. 3. University College London Cancer Institute, London, UK. 4. Istituto Scientifico Romagnolo per Io Studio e La Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 5. Prostate Cancer Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Medical Oncology Department, Hospital Universitario La Princesa, Madrid, Spain. 6. Prostate Cancer Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; CNIO-IBIMA Genitourinary Cancer Unit, Hospitales Universitarios Virgen de Ia Victoria y Regional de Málaga, Instituto de Investigación Biomédica de Málaga, Spain. 7. CNIO-IBIMA Genitourinary Cancer Unit, Hospitales Universitarios Virgen de Ia Victoria y Regional de Málaga, Instituto de Investigación Biomédica de Málaga, Spain. 8. Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), CIBERONC, Madrid, Spain. 9. Medical Oncology Department, Centro Oncológico de Galicia, A Coruña, Spain. 10. Hospital de Mataró, Mataró, Spain. 11. Medical Oncology Department, IDIBAPS, Hospital Clínico y Provincial, Barcelona, Spain. 12. Medical Oncology Department, Gregorio Marañón University Hospital, Madrid, Spain. 13. Medical Oncology Unit, Ospedale Policlinico San Martino, Genoa, Italy. 14. Medical Oncology Unit 1, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy. 15. Department of Hematology & Medical Oncology, Hospital Universitario Morales Meseguer, IMIB-Universidad de Murcia, Murcia, Spain; Universidad Católica San Antonio de Murcia-UCAM, Murcia, Spain. 16. University College London Cancer Institute, London, UK. Electronic address: g.attard@ucl.ac.uk.
Abstract
BACKGROUND: Plasma androgen receptor (AR) copy number status has been identified as a potential biomarker of response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR status in the context of cabazitaxel therapy is unknown. PATIENTS AND METHODS: Between September 2011 and January 2018, pretherapy plasma samples were collected from 155 patients treated with second- or third-line cabazitaxel at standard or reduced dose in different biomarker protocols. Droplet digital polymerase chain reaction was used to identify plasma AR gain and normal samples. The primary objective was to evaluate associations of plasma AR status with treatment outcome. In an exploratory analysis, a comparison between plasma AR and treatment type was investigated by incorporating updated data from our prior study of 85 post-docetaxel patients receiving abiraterone or enzalutamide. RESULTS: We observed a shorter median overall survival (OS) and progression-free survival (PFS) in AR-gained compared to AR-normal patients (OS 10.5 versus 14.1 months, hazard ratio (HR) = 1.44, 95% confidence interval [CI] 0.98-2.13, P = 0.064 and PFS 4.0 versus 5.0 months, HR = 1.47, 95% CI 1.05-2.07, P = 0.024). In patients with mCRPC receiving second-line therapies, a significant treatment interaction was observed between plasma AR and cabazitaxel versus AR-directed therapies for OS (P = 0.041) but not PFS (P = 0.244). In an exploratory analysis, AR-gained patients treated with initial reduced dose of cabazitaxel had a significantly shorter median OS (7.3 versus 11.5 months, HR = 1.95, 95% CI 1.13-3.38, P = 0.016) and PFS (2.7 versus 5.0 months, HR = 2.27, 95% CI 1.39-3.71, P = 0.001). CONCLUSION: Plasma AR status has a potential clinical utility in patients being considered for cabazitaxel. Validation of these findings in prospective trials is warranted.
BACKGROUND: Plasma androgen receptor (AR) copy number status has been identified as a potential biomarker of response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR status in the context of cabazitaxel therapy is unknown. PATIENTS AND METHODS: Between September 2011 and January 2018, pretherapy plasma samples were collected from 155 patients treated with second- or third-line cabazitaxel at standard or reduced dose in different biomarker protocols. Droplet digital polymerase chain reaction was used to identify plasma AR gain and normal samples. The primary objective was to evaluate associations of plasma AR status with treatment outcome. In an exploratory analysis, a comparison between plasma AR and treatment type was investigated by incorporating updated data from our prior study of 85 post-docetaxelpatients receiving abiraterone or enzalutamide. RESULTS: We observed a shorter median overall survival (OS) and progression-free survival (PFS) in AR-gained compared to AR-normal patients (OS 10.5 versus 14.1 months, hazard ratio (HR) = 1.44, 95% confidence interval [CI] 0.98-2.13, P = 0.064 and PFS 4.0 versus 5.0 months, HR = 1.47, 95% CI 1.05-2.07, P = 0.024). In patients with mCRPC receiving second-line therapies, a significant treatment interaction was observed between plasma AR and cabazitaxel versus AR-directed therapies for OS (P = 0.041) but not PFS (P = 0.244). In an exploratory analysis, AR-gained patients treated with initial reduced dose of cabazitaxel had a significantly shorter median OS (7.3 versus 11.5 months, HR = 1.95, 95% CI 1.13-3.38, P = 0.016) and PFS (2.7 versus 5.0 months, HR = 2.27, 95% CI 1.39-3.71, P = 0.001). CONCLUSION: Plasma AR status has a potential clinical utility in patients being considered for cabazitaxel. Validation of these findings in prospective trials is warranted.
Authors: Yuanshuo Alice Wang; John Sfakianos; Ashutosh K Tewari; Carlos Cordon-Cardo; Natasha Kyprianou Journal: Oncogene Date: 2020-10-12 Impact factor: 9.867
Authors: M C Cursano; V Conteduca; E Scarpi; G Gurioli; C Casadei; S Gargiulo; A Altavilla; C Lolli; B Vincenzi; G Tonini; D Santini; U De Giorgi Journal: Sci Rep Date: 2022-05-05 Impact factor: 4.996
Authors: Felipe Couñago; Fernando López-Campos; Ana Aurora Díaz-Gavela; Elena Almagro; Esaú Fenández-Pascual; Iván Henríquez; Rebeca Lozano; Estefanía Linares Espinós; Alfonso Gómez-Iturriaga; Guillermo de Velasco; Luis Miguel Quintana Franco; Ignacio Rodríguez-Melcón; José López-Torrecilla; Daniel E Spratt; Luis Leonardo Guerrero; Juan Ignacio Martínez-Salamanca; Elia Del Cerro Journal: Cancers (Basel) Date: 2020-06-12 Impact factor: 6.639
Authors: A González Del Alba; M J Méndez-Vidal; S Vazquez; E Castro; M A Climent; E Gallardo; E Gonzalez-Billalabeitia; D Lorente; J P Maroto; J A Arranz Journal: Clin Transl Oncol Date: 2021-02-24 Impact factor: 3.405