Combination of PARP Inhibitors and Androgen Receptor Pathway Inhibitors in Metastatic Castration-Resistant Prostate Cancer
- Journal Title
- Drugs
- Publication Type
- Online publication before print
- Abstract
- Despite recent advances in the treatment of metastatic prostate cancer, progression to a castration-resistant state remains inevitable for most and prognosis is limited. Genetic testing for homologous recombination repair pathway alterations is recommended for all patients with advanced prostate cancer given that a mutation is present in up to 25% of cases. Poly(ADP-ribose) polymerase (PARPis) are now approved for use in patients with metastatic castration-resistant prostate cancer who have progressed on an androgen receptor pathway inhibitor (ARPI) and harbour a germline or somatic homologous recombination repair mutation. Preclinical data support a synergistic effect with an ARPI and PARPi, and various ARPI-PARPi combinations have therefore been explored in phase III clinical trials. Despite heterogeneous findings, a clear hierarchy of benefit is evident, with patients harbouring a BRCA mutation deriving the greatest magnitude of benefit, followed by any homologous recombination repair mutation. The benefit in homologous recombination repair-proficient cohort is less clear, and questions remain about whether ARPI-PARPi combination therapy should be offered to patients without a homologous recombination repair mutation. With ARPIs now considered standard-of-care for metastatic hormone-sensitive prostate cancer, ARPI-PARPi combination therapy is currently being explored earlier in the treatment paradigm. The purpose of this review is to discuss the rationale behind ARPI-PARPi combination therapy, summarise the results of key clinical trials, and discuss clinical considerations and future perspectives.
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1007/s40265-024-02071-y
- Open Access at Publisher's Site
https://doi.org/10.1007/s40265-024-02071-y- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-08-29 04:13:48
Last Modified: 2024-08-29 04:22:13