The European Commission ( EC ) has approved the marketing authorisation for Zytiga ( Abiraterone acetate ), a novel, once-daily, oral, androgen biosynthesis inhibitor. Abiraterone acetate is approved, in combination with Prednisone or Prednisolone, for the treatment of metastatic castration-resistant prostate cancer ( mCRPC ) in adult men whose disease has progressed on or after a Docetaxel-based chemotherapy regimen.

Abiraterone acetate is an androgen biosynthesis inhibitor that inhibits the CYP17 enzyme complex which is required for the production of androgens. Androgens ( e.g. testosterone ) are hormones that promote the development and maintenance of male sex characteristics. However, in prostate cancer, androgens can fuel the tumour’s growth. Androgen production primarily occurs in the testes and adrenal glands but, in men with prostate cancer, the tumour tissue is an additional source of androgens
Abiraterone acetate is the first oral treatment for metastatic castration-resistant prostate cancer that inhibits androgen production at all three sources.

Results of the pivotal phase 3, randomised, placebo-controlled, multicentre study showed that at a pre-specified interim analysis, after a follow-up of 12.8 months, treatment with Abiraterone acetate in combination with Prednisone or Prednisolone resulted in a 35.4% reduction in the risk of death ( hazard ratio, HR=0.65; p<0.001 ) and an improvement of 3.9 months in median overall survival ( 14.8 months vs. 10.9 months ) compared to placebo plus Prednisone or Prednisolone.
In an updated analysis ( with follow-up period of 20.2 months ), results were consistent with those from the interim analysis with a 4.6 month improvement in median overall survival between the two arms ( 15.8 months vs 11.2 months; HR=0.74 ) in favour of Abiraterone acetate. The effect of Abiraterone acetate and Prednisone on overall survival was consistent across all subgroups.

In patients who reported significant pain from their disease ( a baseline pain score of 4 or more using the Brief Pain Inventory-Short Form [ BPI-SF ] scale of 0 to 10 ) and with at least one post-baseline pain score, the percentage experiencing pain relief ( at least a 30% reduction from baseline in the BPI-SF worst pain intensity score over 24 hours without any increase in analgesic usage score observed at two consecutive evaluations four weeks apart ) was higher in the Abiraterone acetate group than in the placebo group ( 44% versus 27%, p=0.002 ).

A lower proportion of patients receiving Abiraterone acetate had skeletal-related events compared with those given placebo ( 18% vs 28% at six months, 30% vs 40% at 12 months and 35% vs 40% at 18 months ).
A skeletal-related event was defined as a pathological fracture, spinal cord compression, palliative radiation to bone, or surgery to bone.

The most common adverse reactions seen with Abiraterone acetate are peripheral oedema, hypokalaemia, hypertension and urinary tract infection.

Source: Janssen-Cilag, 2011

XagenaMedicine2011


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