Despite most metastatic castration-resistant prostate cancer (mCRPC) patients benefit from abiraterone acetate plus prednisone 5 mg bid (AA + P), resistance eventually occurs. Long-term use of prednisone has been suggested as one of the mechanisms driving resistance, which may be reversed by switching to another steroid.
SWITCH was a single-arm, open-label, single-stage phase II study. The primary objective was to evaluate the antitumour activity of abiraterone acetate plus dexamethasone 0.5 mg daily (AA + D) in mCRPC patients progressing to AA + P. Clinically stable mCRPC patients who had prostate-specific antigen (PSA) and/or limited radiographic progression after at least 12 weeks on AA + P, were eligible. The primary endpoint was measured as the proportion of patients achieving a PSA decline of ≥ 30% (PSA30) from baseline after 6 weeks on AA + D. Secondary endpoints included: PSA50 response rate at 12 weeks, time to biochemical and radiological progression, overall survival, safety profile evaluation, benefit from subsequent treatment lines and the identification of biomarkers of response (AR copy number, TMPRSS2-ERG status and PTEN expression).
Twenty-six patients were enrolled. PSA30 and PSA50 were 46.2% and 34.6%, respectively. Median time to biochemical and radiological progression were 5.3 and 11.8 months, respectively. Two radiological responses were observed. Median overall survival was 20.9 months. Patients with AR gain detected in plasma circulating tumour DNA did not respond to switch, whereas patients with AR normal status benefited the most. No significant toxicities were observed and PSA50 response rate to subsequent taxane was 50%.
In selected clinical stable mCRPC patients with limited disease progression on AA + P, a steroid switch from prednisone to dexamethasone can lead to PSA and radiological responses.
British journal of cancer. 2018 Aug 21 [Epub]
Nuria Romero-Laorden, Rebeca Lozano, Anuradha Jayaram, Fernando López-Campos, Maria I Saez, Alvaro Montesa, Ana Gutierrez-Pecharoman, Rosa Villatoro, Bernardo Herrera, Raquel Correa, Adriana Rosero, María I Pacheco, Teresa Garcés, Ylenia Cendón, Ma Paz Nombela, Floortje Van de Poll, Gala Grau, Leticia Rivera, Pedro P López, Juan-Jesús Cruz, David Lorente, Gerhardt Attard, Elena Castro, David Olmos
Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Division of Molecular Pathology, Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom., CNIO-IBIMA Genitourinary Cancer Research Unit, Institute of Biomedical Research in Málaga (IBIMA), Málaga, Spain., Medical Oncology Department, Hospital Universitario de La Princesa, Madrid, Spain., Medical Oncology Department, Hospital Universitario de Salamanca, Salamanca, Spain., Medical Oncology Department, Hospital Universitario La Fe, Valencia, Spain., Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. .