Single institution long-term efficacy and safety analysis of abiraterone acetate (AA) in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) in a named patient programme (NPP).

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.

Table 1

Univariate analysis of pretreatment and treatment-related factors for PSA-PFS and OS

	PSA-PFS		OS
	HR (95% CI)	p Value	HR (95% CI)	p Value
Age (years)
<65	1		1
≥65	0.62 (0.19 to 2.09)	0.44	0.60 (0.26 to 1.33)	0.21
Baseline ECOG performance status
0–1	1		1
2	2.55 (0.76 to 8.51)	0.13	4.04 (1.58 to 10.30)	0.004
Baseline Gleason score
≤7	1		1
≥8	0.85 (0.25 to 2.80)	0.79	1.39 (0.55 to 3.54)	0.49
Pre-AA PSA
<87	1		1
≥87	0.27 (0.06 to 1.29)	0.1	1.56 (0.57 to 4.28)	0.39
Metastatic at initial presentation
Yes	1		1
No	0.84 (0.29 to 2.43)	0.74	1.0 (0.38 to 2.67)	0.99
Duration of hormonal therapy (months)
<16	1		1
≥16	1.96 (0.62 to 6.18)	0.25	0.37 (0.14 to 0.99)	0.05
Previous lines of chemotherapy
1	1		1
2	0.52 (0.19 to 1.42)	0.2	0.62 (0.27 to 1.43)	0.27
PSA response
Yes	1		1
No	27.67 (3.37 to 227.01)	0.002	3.10 (1.29 to 7.46)	0.01
Sites of metastasis
Bone	1		1
Lymph node	0.72 (0.22 to 2.31)	0.58	0.18 (0.04 to 0.78)	0.022

Statistically significant p values are shown in bold.

AA, abiraterone acetate; ECOG, Eastern Cooperative Oncology Group; OS, overall survival; PSA, prostate-specific antigen; PFS, progression-free survival.

Figure 1

Impact of (A): metastatic sites (bone metastasis±lymph node metastasis vs visceral metastasis), (B): PSA response, (C): AA drug exposure duration on overall survival. AA, abiraterone acetate; PSA, prostate-specific antigen.

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.