Abiraterone: A Breakthrough for Men with Prostate Cancer

Approved by FDA– April 2011

Trade name– Zytiga 250 mg

Medicinal form– White or off-white oval tablets

Why is it taken?

Along with prednisone, it is given alongside androgen deprivation therapy for newly diagnosed metastatic prostate cancer when surgery doesn’t have a curative effect.

Who shouldn’t take the drug?

1. Pregnant ladies
2. Patients with severe hepatic impairment
   

Serious expected drug reactions

1. Hypertension
2. Hypercalemia
3. Fluid retention
4. Cardiac failure
5. Increase in biliary and hepatic enzymes
   Which is why you take this with a corticosteroid.
   

How does it work?

Abiraterone is an irreversible and selective inhibitor of 17 α 17α-hydroxylase/C17,20-lyase (CYP17), an enzyme highly expressed in testicular, adrenal, and prostate cancer. This enzyme is involved in androgen (a precursor to male hormone- testosterone) biosynthesis. Abnormal levels of androgens are implicated in prostate cancer.

Latest research

1) Survival outcomes with abiraterone (mHSPC, meta-analysis; n=3,374)

• Abiraterone improved overall survival (OS HR 0.66) and progression-free survival (PFS HR 0.51)
• The benefit was consistent in both low- and high-volume disease.
• Safety: fewer grade 1–2 AEs, but more grade 3–4 AEs.
• Takeaway: Abiraterone works across disease volumes; monitor closely for severe AEs.
  

2) Abiraterone + trastuzumab deruxtecan (T-DXd) in HER2-expressing mCRPC (case report)

•  HER2 expression (~60–70%) in mCRPC may drive resistance to androgen-targeted therapy.
• A patient who had progressed on abiraterone showed a significant response when re-challenged with abiraterone + T-DXd.
• In prostate cancer, HER2 overexpression often occurs without mutations/amplifications, so it’s missed by NGS.
• We can use HER2 IHC (not routinely done) to identify candidates.
• Takeaway: The T-DXd + abiraterone combo may help overcome resistance in HER2-positive mCRPC; consider routine HER2 IHC testing in advanced cases.