Combination of PARP Inhibitors and Androgen Receptor Pathway Inhibitors in Metastatic Castration-Resistant Prostate Cancer

Kostos, L; Tran, B; Azad, AA

Author(s): Kostos, L; Tran, B; Azad, AA;
Details: Publication Year 2024-09,Volume 84,Issue #9,Page 1093-1109
Journal Title: Drugs
Publication Type: Review
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.
Publisher: Springer Nature
Keywords: Humans; Male; *Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use/pharmacology; *Prostatic Neoplasms, Castration-Resistant/drug therapy/pathology; *Androgen Receptor Antagonists/therapeutic use/pharmacology; Receptors, Androgen/metabolism/genetics; Antineoplastic Combined Chemotherapy Protocols/therapeutic use/pharmacology; Neoplasm Metastasis
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: 2024-10-23 05:59:30

Last Modified: 2024-10-23 05:59:43