Enzalutamide Extends Metastatic, Castration-Resistant Prostate Cancer PFS Over Bicalutamide

Enzalutamide 160 mg/day offers longer progression-free survival than bicalutamide 50 mg/day for men with metastatic, castration-resistant prostate cancer in a phase II study

medwireNews: TERRAIN results support the use of enzalutamide for the treatment of metastatic, castration-resistant prostate cancer patients with no or minimal symptoms, demonstrating significant benefits over bicalutamide .

Median investigator-based progression-free survival (PFS) in the phase II trial was significantly longer in the 184 men randomly assigned to receive enzalutamide 160 mg/day plus androgen-deprivation therapy (ADT) than the 191 men given bicalutamide 50 mg/day plus ADT, at 15.7 versus 5.8 months and a hazard ratio (HR) of 0.44.

This was true when patients were assessed by subgroups of age, geographical location (North American or Europe), performance status on entry to the trial, timing of ADT initiation and history of anti-androgen treatment, say Neal Shore, from Carolina Urologic Research Center in Myrtle Beach, South Carolina, USA, and co-authors.

Nevertheless, the researchers admit that the TERRAIN findings are limited by the absence of overall survival analysis.

“Additionally, given that patients included in this study are from specific geographical regions and that the bicalutamide dose used in this study corresponds to that used in specific regions, the findings of TERRAIN are not generalisable to patient populations in other locations or regions that use a different bicalutamide dose”, they observe.

As reported in The Lancet Oncology, the median time to radiographical progression was not reached in the men given the androgen receptor inhibitor enzalutamide versus 16.4 months for those using the nonsteroidal anti-androgen agent bicalutamide, giving a significant HR of 0.51.

And enzalutamide-treated men took a median of 19.4 months to have their first prostate-specific antigen (PSA) progression event compared with just 5.8 months for those given bicalutamide (HR=0.28).

Indeed, a 50% or greater PSA decline was achieved by 82% versus 21% of the enzalutamide and bicalutamide treatment groups, respectively, with a significantly greater median change by week 13 for the former.

Enzalutamide also conferred a significantly longer time to Functional Assessment of Cancer Therapy–Prostate (FACT-P) total score deterioration than bicalutamide, at a median of 13.8 versus 8.5 months, as well as greater rates of improvement in some FACT-P domains, and the total scores for FACT-P and the Functional Assessment of Cancer Therapy–General questionnaires.

Grade 3 or more severe adverse events were reported in 40% of the enzalutamide and 38% of the bicalutamide groups , and included hypertension (7 vs 4%), hydronephrosis (2 vs 4%), back pain (3 vs 2%), pathological fracture (3 vs 1%), bone pain (1 vs 2%) and dyspnoea (2 vs 1%).

In addition, 3% of the enzalutamide-treated patients experienced myocardial infarction, 2% congestive heart failure and 2% anaemia, compared with a respective 0%, 1% and 0% of the bicalutamide group.

Overall rates of grade 3 or higher cardiac adverse events were 5% versus 2% in the enzalutamide and bicalutamide groups, respectively, but the team notes this occurred more than 6 months into the trial “when there was a greater imbalance in exposure by treatment group”.

Reference

Shore ND, Chowdhury S, Villers A, et al. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol 2016; Advance online publication 13 January. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00518-5

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