Abiraterone acetate tied to favourable outcomes in prostate cancer treatment
Abiraterone acetate (AA) was associated with improved survival outcomes in prostate cancer treatment and had a favourable toxicity profile, according to several studies presented at the ASCO Genitourinary Cancers Symposium 2018 (ASCO GU 2018).
Two studies demonstrated the efficacy of AA in improving survival outcomes in prostate cancer when added to androgen deprivation therapy (ADT) and prednisone.
According to a meta-analysis comprising five studies (n=4,462), the addition of AA or docetaxel to ADT reduced the risk of developing castration resistance among men with metastatic castration-sensitive prostate cancer (mCSPC, hazard ratio [HR], 0.47, 95 percent confidence interval [CI], 0.33–0.67), translating to an increased castration-resistance free survival (CFS) rate. [ASCO GU 2018, abstract 354]
The subgroup analysis revealed better CFS rates with AA vs docetaxel (HR, 0.31 vs HR, 0.62; p<0.001), which highlights the potential of AA as initial therapy for mCSPC, said the researchers.
In terms of toxicity however, AA was associated with an increased risk of hypokalaemia (HR, 6.63, 95 percent CI, 3.5–12.5) and cardiac toxicity (HR, 2.4, 95 percent CI, 1.7–3.3).
Similar survival and safety outcomes were observed in the randomized LATITUDE* trial comprising 1,199 patients with newly diagnosed, high-risk metastatic castration-naïve prostate cancer (mCNPC). [ASCO GU 2018, abstract 182]
Individuals who received an AA and prednisone (AAP) combination plus ADT had improved overall survival (HR, 0.62, 95 percent CI, 0.51–0.76; p<0.0001) and radiographic progression-free survival (HR, 0.47, 95 percent CI, 0.39–0.55) compared with those who received ADT plus placebo.
Safety analysis revealed an increased risk of mineralocorticoid excess (ME)-related adverse events (AEs) such as hypertension (relative risk, 1.6, 95 percent CI, 1.4–1.9) and grade 3/4 hypokalaemia (10.4 percent vs 1.3 percent) among AAP-ADT vs placebo-ADT recipients.
Nonetheless, most AAP-ADT recipients with grade 3/4 hypertension and hypokalaemia progressed to grade ≤2 (87 percent and 89 percent, respectively), with most hypertension events being controlled by supplemental antihypertensive agents. Furthermore, <1 percent of participants in either arm discontinued treatment due to ME-related AEs.
“[Our findings] confirm the safety of [AAP plus] ADT and helps provide practical treatment guidance for managing mCNPC,” said the LATITUDE investigators.
The multicentre, phase IV, prospective REAAcT** study supported these safety outcomes, with fewer AEs (36 percent vs 52 percent) and fatigue-related AEs (8 percent vs 26 percent) associated with AAP vs enzalutamide in patients with metastatic castration-resistant prostate cancer (n=92, median age 75 years). [ASCO GU 2018, abstract 296]
Additionally, REAAcT demonstrated better neurocognitive outcomes associated with AAP vs enzalutamide, with only one patient receiving AAP showing a clinically significant cognitive decline at 2 months, as opposed to four in the enzalutamide arm.
The improved survival rates and manageable toxicities are consistent with previous studies supporting the long-term use of AA for prostate cancer treatment. [Clin Cancer Res 2011;17:4854-4861; N Engl J Med 2011;364:1995-2005] Furthermore, given evidence showing androgen levels sufficient for driving tumour growth even after surgical castration, the results also underscore the role of AA in pre-chemotherapy treatment in castration-resistant prostate cancer cases. [Clin Cancer Res 2005;11:4653-4657; N Engl J Med 2013;368:138-148]