Shahneen Sandhu, MBBS, FRAPC, Peter MacCallum Cancer Centre, Victoria, Australia, shares insights from the PREVALANCE study. This study evaluated the frequency of homologous recombination repair (HRR) gene alterations among patients with metastatic castration-sensitive and castration-resistant prostate cancer. Of 14073 patients with at least 1 result by assay, 14% had at least 1 mutation in HRR genes of interest and the frequency of alterations were similar for both castration-sensitive and castration-resistant prostate cancers.

Dr Sandhu concluded, “This data is important because it shows that we can identify these men by genetic testing. And genetic testing is important, because there is now effective treatment for these men that have these alterations, and it can significantly improve their outcome.”

These results were first presented at the 2023 European Society for Medical Oncology Annual Congress in Madrid, Spain.

Transcript:

Hello from ESMO 2023. My name is Associate Professor Shahneen Sandhu from the Peter MacCallum Cancer Center in Melbourne, Australia. Today, I'd like to share with you some exciting data from the PREVALENCE clinical trial.

One of the things we understand is that prostate cancer is highly heterogeneous at a molecular level, and molecular profiling of these cancers has led to us being able to deliver targeted therapies to these patients. In particular, approximately 20% to 30% of men with advanced prostate cancer will harbor an underlying DNA repair defect, namely BRCA1 and BRCA2 alterations. And these men, unfortunately, have a more aggressive disease biology and a worse clinical outcome, despite the fact that they're receiving standard therapies. Thankfully, these men with underlying DNA repair defects, in particular the BRCA1 and BRCA2 patients, have tumors that are highly sensitive to PARP inhibition and can benefit significantly from this treatment.

We undertook a clinical trial that is called PREVALENCE, and the intent of this study was ambitious and was intended to try to identify the prevalence of these DNA repair defects in men with advanced cancer across multiple regions globally. The study was undertaken at 319 sites in 23 countries, and approximately 14 000 patients were enrolled. Patients were consented, and they provided a saliva sample, a blood sample, and tissue material. These were subjected to sequencing to identify these alterations. We found that the tumor material resulted in identifying most of these alterations, then it was the blood or circulating tumor DNA, followed by a saliva or what we call germline, or inherited genetic material.

The incidence of these DNA repair defects, or homologous recombination DNA repair defects, was approximately 15%, and it was very similar across the countries and regions. It was slightly higher in Europe, compared to the other regions. When we look at that group of men with homologous recombination repair defects, it was largely made up of BRCA, in particular BRCA2, followed by ATM, CHEK2, CDK12, PALB2, and BRCA1.

This data is important, because it shows that we can identify these men by genetic testing. And genetic testing is important, because there is now effective treatment for these men that have these alterations. And it can significantly improve their outcome.

Source:

Sandhu SK, Gotto G, Vera-Badillo FE, et al. A prospective study to determine the prevalence of DNA repair defects in patients (pts) with advanced prostate cancer (PC). Presented at 2023 ESMO Annual Congress; October 20-24, 2023; Madrid, Spain. 1835P