PARP-remmers bij gemetastaseerde prostaatkanker: een systematische review

Abstract

PARP inhibitors in metastatic prostate cancer: a systematic review Background. Poly ADP-ribose polymerase (PARP) inhibitors provide a novel therapeutic approach for the treatment of metastatic prostate cancer. They act on the homologous recombination DNA repair mechanism. In metastatic prostate cancer, 20-25% of the patients harbour a homologous recombination repair deficiency. This review investigates the current evidence for the use of PARP inhibitors in clinical practice. Methods. The databases MEDLINE, CENTRAL and EMBASE were searched, as well as the clinical trial registries EudraCT and Clinicaltrials.gov. Randomised controlled trials with PARP inhibitors were included. The outcomes of interest were: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), adverse events and quality of life. The data were analysed according to Cochrane methodology. Results. Three controlled trials were included, all in a castration-resistant setting. Five phase 2 trials were excluded; these data are presented in a narrative form. One study of olaparib in monotherapy versus enzalutamide or abiraterone found a benefit in OS and PFS in patients with a BRCA1, BRCA2 or ATM mutation, though not in patients with other HRD (‘homologous recombination deficiency’) mutations. Two studies investigated a PARP inhibitor in combination with abiraterone versus abiraterone in monotherapy. The combination with olaparib showed a modest PFS benefit, whereas the veliparib combination showed no OS or PFS benefit. Conclusion. At present, the role of PARP inhibitors is limited to BRCA1, BRCA2 and ATM mutation carriers. Combination therapy with other agents could provide a synergistic advantage and is being researched. Fourteen ongoing trials meet the inclusion criteria and will clarify the role of PARP inhibitors in the treatment of prostate cancer.