Reviews
PARP Inhibitors in Metastatic Prostate Cancer: Evidence Across mCRPC and mHSPC Disease States
McKendry et alClinical advances in hematology & oncology : H&O
Poly(ADP-ribose) polymerase inhibitors (PARPis) represent an established treatment class for patients with homologous recombination repair (HRR) gene-altered metastatic prostate cancer. Clinical efficacy for PARPis—both as monotherapies and in combination with androgen receptor pathway inhibitors (ARPIs)—was first established in metastatic castration-resistant prostate cancer (mCRPC, also designated androgen pathway modulation-resistant [APMR] prostate cancer), with the greatest clinical benefit observed in patients harboring BRCA2 alterations.
More recently, evidence has demonstrated the benefit of combining PARPis with standard-of-care ARPIs and androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC, also designated androgen pathway modulation-sensitive [APMS] prostate cancer), supported by data from the AMPLITUDE and TALAPRO-3 trials evaluating niraparib and talazoparib, respectively.
The extent to which PARPis become integrated into routine clinical management for mHSPC/APMS will depend on resolving key implementation challenges, including refining patient eligibility through biomarker selection, monitoring short- and long-term treatment-related adverse events, evaluating competing treatment modalities, and optimizing therapeutic sequencing. Future therapeutic directions within mHSPC/APMS include the ongoing EvoPAR-Prostate01 phase 3 registration trial, which is evaluating the PARP1-selective inhibitor saruparib.
Key Takeaways
- In metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations, PARP inhibitors—administered as monotherapy or in combination with androgen receptor pathway inhibitors—confer the greatest benefit in BRCA2-altered disease.
- Evidence from the AMPLITUDE and TALAPRO-3 trials demonstrates clinical benefit when combining PARP inhibitors (niraparib and talazoparib, respectively) with standard-of-care androgen receptor pathway inhibitors and androgen deprivation therapy in metastatic hormone-sensitive prostate cancer.
Read the original sourceClinical advances in hematology & oncology : H&O