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Abiretrone acetate (AA) administration in patients with metastatic castration-resistant prostate cancer (mCRPC) results in powerful androgen depletion and consequential reversal of the castrate-resistant state. This translates into the improved survival observed in large phase III trials, with AA given in combination with prednisone either before or after docetaxel chemotherapy.1 ,2 As wide-access studies regularly fail to replicate the same findings as those from large registrational trials, we sought to investigate the long-term efficacy and safety of AA in an unselected population of patients with mCRPC that may be more representative of a real-life clinical setting.3
After publication of the CUO-AA-301 trial in 2011, and before regulatory approval by the European Medicines Agency, AA was made available in Croatia through a named patient programme (NPP), approved by the local hospital ethics committee.1 Within our institution, we prospectively reviewed clinical records of patients with mCRPC treated with AA to assess progression-free survival (PFS), overall survival (OS) and the toxicity profile. All patients eligible for AA had progressed on previously received docetaxel-based chemotherapy. PFS and OS were analysed using the Kaplan-Meier method, while toxicity was graded using Common Terminology Criteria for Adverse Events (CTCAE) V.4. The Cox proportional hazard model was used to assess the association of different clinical parameters with PFS and OS.
Results are summarised in table 1: thirty patients, from April 2012 to April 2014, received treatment with AA and prednisone in a single institution. Median patient age was 69 years (range 55–81 years), and median Eastern Cooperative Oncology Group performance status was 1. Median baseline (pre-AA) prostate-specific antigen (PSA) was 86.5 ng/mL (range 17.5–1868). Twenty-three patients (77%) had bones as the only site of metastases; four patients (13%) had lymph node metastases in addition to bone metastases; 2 patients (7%) had visceral metastases in addition to bone metastases; and 1 patient (3%) had multiple lymph nodes as the only sites of metastatic disease. Twenty-three patients (77%) received no local therapy for primary tumour. The median administered docetaxel chemotherapy cycle was 6 (range 2–16) and median duration of response to primary androgen deprivation therapy was 8 months (range 3–32 months). The median duration of AA treatment was 8 months (range 1–36 months). No co-medications such as bisphosphonates and denosumab were administered. After a median follow-up of 35 months, median PFS and OS were 5 months (95% CI (4–14 months)) and 14.0 months (95% CI (11.0 to 21.0)), respectively. Seventeen patients (57%) experienced PSA response (≥50% reduction in PSA). Factors associated with longer OS were PSA response (HR 0.39 (95% CI (0.16 to 0.96), p=0.04) and AA drug exposure duration (HR 0.9 (95% CI 0.86 to 0.96), p=0.0003), while presence of visceral metastasis was associated with worse OS (HR 6.84 (95% CI 1.31 to 35.5), p=0.02), figure 1. Grade 3 side effects were: anaemia (3 patients), pneumonia (2 patients) and cardiac failure (1 patient). After progression on AA, 2 patients (6%) received docetaxel re-challenge chemotherapy and 1 patient (3%) received cabazitaxel chemotherapy.
The mature PFS, OS and toxicity observed in our population of patients with mCRPC treated with AA provided by NPP are similar to the PFS, OS and toxicity reported in the registrational trial and in other NPP observational studies, indicating long-term efficacy and safety of AA administered in unselected patient populations.4
Our results are a valuable addition to the growing body of evidence on efficacy and safety of AA in the treatment of patients with mCRPC, which justifies this costly therapy even in low-income countries.
Contributors AF and JM were responsible for the conception and design of the study. AF was responsible for preparing study materials of patients. JM was involved in collection and assembly of data. AF and SR assisted in analysis and interpretation of data. All the authors were involved in writing of the manuscript and its final approval.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Institutional Review Board approval obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.
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