Episode 14: Improved clinical outcomes with the combination of olaparib and abiraterone-acetate in the 1st line treatment of metastatic CRPC

In this new episode of WND Prostate cancer, Prof Bertrand Tombal from the Cliniques Universitaires Saint-Luc in Brussels and Prof Steven Joniau from the University Hospitals Leuven share their thoughts on the results of the phase III PROpel study, a trial that evaluated the PARP inhibitor olaparib as part of the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC)

The first study to show a potential role for PARP inhibition in prostate cancer was the phase III PROfound trial. In this trial, olaparib proved to be associated with a significant benefit in progression-free (PFS) and overall survival (OS) in heavily pretreated patients with mCRPC.¹ Building further on these findings, the randomized, phase III PROpel study compared a combination of abiraterone acetate (AA) and olaparib to AA alone as first line treatment for unselected patients with mCRPC.²

Irrespective of the BRCA mutation status of patients, the addition of olaparib to AA led to a significant improvement in radiographic PFS. However, this PFS benefit proved to be much more pronounced in the subgroup of patients with a BRCA mutation in whom the delayed disease progression also translated into a dramatic benefit in OS (median OS not reached vs. 23.0 months; HR[95%CI]: 0.29[0.14-0.56]). While it was interesting to see that the addition of olaparib also delayed disease progression in BRCA wildtype patients, this benefit did not lead to a longer OS for these patients (median OS 39.6 vs. 38.0 months; HR[95CI]: 0.91[0.73-1.13]).²

For Prof Joniau and Prof Tombal, these results underscore that PARP inhibition is here to stay in prostate cancer and that early BRCA mutation testing should therefore be an integral part of the management of patients with prostate cancer.