Abiraterone acetate and prednisone in the pre- and post-docetaxel setting for metastatic castration-resistant prostate cancer: a mono-institutional experience focused on cardiovascular events and their impact on clinical outcomes

Abstract

Background:The aim of this work was to to evaluate the incidence and risk factors of adverse events (AEs), focusing on cardiovascular events (CVEs) and hypokalemia, in patients treated with abiraterone acetate (AA) and prednisone (PDN) outside clinical trials, and their association with survival outcomes.Methods:This was a retrospective cohort study of 105 patients treated from 2011 to 2016. Incidence of AEs was descriptively summarized in the whole cohort and by subgroup (pre- versus post-docetaxel). Multivariable Cox proportional hazards models assessed factors associated with progression-free survival (PFS) and overall survival (OS).Results:Overall, median PFS and OS were 14.9 and 24.6 months, respectively. Prostate-specific antigen (PSA) ⩾ 10 ng/ml (p = 0.007), Gleason Score >7 (p = 0.008), Eastern Cooperative Oncology Group (ECOG) performance status (PS)1–2 (p = 0.002), duration of androgen deprivation therapy (ADT) ⩽ 43.2 months (p = 0.01), and body mass index (BMI) > 25 (p = 0.03) were associated with worse PFS; presence of pain (p = 0.01), ECOG PS1–2 (p = 0.004), duration of ADT ⩽ 43.2 (p = 0.05), and BMI > 25 (p = 0.042) were associated with worse OS. Incidence of CVEs was as follows: hypertension 17.1%, fluid retention 4.8%, cardiac disorders 8.6%. 16.2% of patients developed hypokalemia. Age ⩾ 75 years was associated with higher probability of cardiac disorders (p = 0.001) and fluid retention (p = 0.03). CVEs did not impact on PFS or OS. Hypokalemia was associated with better median OS (p = 0.036). Similar associations were observed after stratification by subgroup.Conclusions:Median PFS and OS estimates and incidence of CVEs and hypokalemia in our series are consistent with those of pivotal trials of AA plus PDN, confirming the efficacy and safety of this regimen also in the real-world setting. Elderly patients have higher odds of developing/worsening CVEs. However, regardless of age, CVEs were not associated with worse outcomes. Treatment-related hypokalemia seemed to be associated with longer OS, albeit this finding needs confirmation within larger, prospective series.

Effectiveness of abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer in a large prospective real-world cohort: the ABItude study

“…In agreement with previous real-world studies, 18 , 20 , 22 , 24 – 26 , 28 , 37 , including Italian ones, 21 , 27 our findings confirm, in a real-life setting, the efficacy and safety of abiraterone demonstrated in the registration trial (COU-AA-302), despite the poorer clinical features of the enrolled patients, including the advanced age (60% of our patients were ⩾75 years old) and the high prevalence of comorbidity.…”

“…Abiraterone was well tolerated in our cohort of elderly patients with pre-existing cardiac disorders, in line with previous real-life observations. 21 , 44 – 46 In the largest study published so far by Boegemann et al ., 22 2% of patients discontinued due to toxicity, 8% of patients had an ADR and <1% had a serious ADR. In our study similar numbers were reported: discontinuation of therapy because of toxicity occurred in 5% of patients, and 13% of patients had an ADR; only 1.7% reported a serious ADR.…”

Key Role of Obesity in Genitourinary Tumors with Emphasis on Urothelial and Prostate Cancers

“…A few years ago, Cavo et al evaluated the correlation between risk factors of adverse events and survival outcomes in mCRPC patients treated with abiraterone acetate and prednisone, observing that at multivariable analysis BMI >25 kg/m 2 resulted significantly associated both with worse progression-free survival and worse overall survival (OS) ( p = 0.03 and p = 0.042, respectively) [94]. Furthermore, a research group headed by Antoun retrospectively analyzed whether body composition parameters affected prognosis of mCRPC patients treated with androgen receptor inhibitors abiraterone acetate and enzalutamide into two prospective clinical trials [95,96], showing that no relationship between BMI and OS was detected [97].…”

Potential impact of combined inhibition of 3α-oxidoreductases and 5α-reductases on prostate cancer

“…However, inhibition of CYP17A1 by abiraterone can lead to glucocorticoid insufficiency and mineralocorticoid excess. Hypertension, hypokalemia and peripheral edema occur with sufficient frequency that abiraterone is co-administered with prednisone [34] , [35] , [36] .…”