Which data on metastatic castration-resistant prostate cancer (mCRPC) garnered attention at this year’s American Society of Clinical Oncology (ASCO) conferences? This roundtable features Dr Neeraj Agarwal (USA) , Professor Axel Merseburger (Germany) , Professor Karim Fizazi (France) , and Dr Bárbara Vieira Lima Aguiar Melão (Brazil) . They provide expert analysis of standout sessions from the 2024 ASCO Annual Meeting (ASCO 2024) and the 2024 ASCO Genitourinary Cancers Symposium (ASCO GU 2024).
PARP inhibitors in focus for mCRPC
- So with that, we'll go back to Dr. Fizazi. So, Karim, this is a trial, is a phase two study of induction docetaxel and carboplatin in patients with mCRPC with homologous recombination and DNA repair deficiency followed by maintenance therapy with rucaparib, so I thought that trial design was interesting. Please, would you like to share your views on this abstract?
Dr Agarwal (Huntsman Cancer Institute, University of Utah, Salt Lake City, USA) discusses key clinical trials in mCRPC covered at ASCO 2024, focusing on poly-ADP ribose polymerase inhibitors (PARPi). View transcript.
PARPi therapy is a relatively recent addition to the armamentarium of treatments for mCRPC. Hear about the clinical implications of PARPi-focused trials presented at ASCO 2024, with Professor Merseburger (University Hospital Schleswig-Holstein, GermanView transcript.
- So, we'll move on to the PARP inhibitor abstracts, and before I do that, I'd like to share some of the background information before we delve into discussion of these trials. So, last year, actually last year and early this year, we saw several abstracts or publications happening in the first-line mCRPC setting, combining PARP inhibitor with ARPIs. One trial was PROpel trial, which randomised hundreds of patients to abiraterone plus minus olaparib, and we saw another trial, TALAPRO-2 trial, where patients were randomised to enzalutamide plus minus talazoparib. There was another trial with abiraterone plus minus niraparib, and all were in first-line mCRPC setting, and we saw data from the PROpel and TALAPRO-2 trial, which both included patients who were selected for homologous recombination repair mutations and who were not selected for homologous recombination repair mutations to varying degree in these trials. I won't go into the nuances of these trials for our discussion today, but overall, the message was that combination of ARPI and PARP inhibitor had striking benefit in patients with BRCA1 and BRCA2 mutations in the mCRPC setting. Also, the efficacy was present with a hazard issue about 0.5 in patients who had homologous recombination repair mutations, and there was some efficacy, although with a lesser magnitude, in patients who were not selected or who did not harbour these DNA-repair gene mutations. And then there was BRCAWAY trial presented by Dr. Maha Hussain in the GU ASCO 2024 meeting. It was a smaller investigator-initiated clinical trial which asked a question not asked by any of these phase three trial, which was in the first line MCRP setting what happens with the combo of ARPI plus PARP inhibitor when it compares, when you compare the combination with single agent PARP inhibitor.
How do findings from randomised trials in mCRPC translate to the real world? Dr Agarwal compares and contrasts evidence on olaparib. View transcript.
- There was an abstract from a community-based practise, AI concert oncology 144 patient data from real-world patients. And these are the patients who had mCRPC and they had homologous recombination of mutations. And the reason we included this abstract is to basically talk about the real world results with PARP inhibitors and how they compare with the registration trials. So, just for our listeners' recollection, profound was the first phase three trial, where patients were selected based on a biomarker and it was positive. And then in this trial, Olaparib, a PARP inhibitor, was compared with a alternate ARPI in patients who had disease progression on a prior ARPI. And they could have received docetaxel chemotherapy, and many patients did. And in this trial, in patients with BRCA 1, BRCA 2, and ATM mutations, treatment with Olaparib significantly improved radiographic progression-free survival, about 60% reduction, risk of progression, and improved overall survival with about 30% reduction in risk of death despite 80% crossover.
