Olaparib monotherapy or in combination with abiraterone for treating mutated metastatic castration-resistant prostate cancer: alone or stronger together?

Expert Opin Investig Drugs. 2024 Oct;33(10):993-999. doi: 10.1080/13543784.2024.2391828. Epub 2024 Aug 20.

Abstract

Introduction: Prostate cancer has entered the era of precision medicine with the introduction of PARP inhibitors for patients with specific mutations in genes associated with DNA damage repair. Recent studies have shown benefit in combination therapy with PARP inhibitors like olaparib and antiandrogens like abiraterone.

Areas covered: This review discusses the pharmacodynamics and pharmacokinetics of olaparib as well as the data supporting combination therapy with olaparib and abiraterone.

Expert opinion: Co-targeting the androgen receptor and PARP pathway has shown clear clinical benefit in the management of patients with metastatic castration resistant prostate cancer and mutations in BRCA1, BRCA2, and ATM. The benefit in patients without these mutations is less clear, and the benefit of olaparib combination therapy in the management of hormone sensitive disease remains to be seen.

Keywords: BRCA; DNA damage repair; Olaparib; PARP inhibitor; prostate cancer.

Publication types

  • Review

MeSH terms

  • Androgen Antagonists / administration & dosage
  • Androgen Antagonists / pharmacology
  • Androstenes* / administration & dosage
  • Androstenes* / pharmacology
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / pharmacology
  • Humans
  • Male
  • Mutation*
  • Neoplasm Metastasis
  • Phthalazines* / administration & dosage
  • Phthalazines* / pharmacology
  • Piperazines* / administration & dosage
  • Piperazines* / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors* / administration & dosage
  • Poly(ADP-ribose) Polymerase Inhibitors* / pharmacology
  • Precision Medicine
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / genetics
  • Prostatic Neoplasms, Castration-Resistant* / pathology

Substances

  • abiraterone
  • Piperazines
  • olaparib
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Androstenes
  • Phthalazines
  • Androgen Antagonists