Dr Gong on the Importance of Molecular Profiling in mCRPC

Jun Gong, MD, associate professor, medicine, medical oncologist, Gastrointestinal Disease Research Group, Pancreatic Cancer Research Group, Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai, discusses the importance of molecular profiling when determining optimal treatment approaches for patients with metastatic castration-resistant prostate cancer (mCRPC), as well as which PARP inhibitor–based regimens are indicated for patients with specific mutational profiles.

The emergence of targeted therapies in the mCRPC treatment paradigm underscores the necessity of next-generation sequencing and molecular profiling, especially as several PARP inhibitor–based combinations are indicated for patients with specific mutational profiles, Gong says. To identify candidates for these PARP inhibitor combinations, oncologists can order germline or genetic testing, both of which are recommended by the National Comprehensive Cancer Network guidelines for patients with metastatic prostate cancer, Gong notes. Somatic testing via tissue biopsies or liquid biopsies, such as circulating tumor DNA–based assays, can also be employed to detect DNA damage repair mutations, according to Gong.

Knowledge of patients’ treatment history is also crucial when determining the optimal treatment regimen, Gong explains. Currently, all PARP inhibitor–based combinations that are FDA approved for the treatment of patients with CRPC are indicated for the frontline metastatic setting. However, ongoing research is investigating the use of these regimens earlier in the disease course for patients with metastatic castration-sensitive prostate cancer, Gong adds. Identifying driver mutations at early stages of advanced prostate cancer through somatic or liquid-based testing is therefore crucial, Gong says.

Once mutations are confirmed, patients need to be stratified based on the type of DNA damage repair mutation they display, Gong emphasizes. For patients with BRCA1/BRCA2-mutated mCRPC, all 3 FDA-approved PARP inhibitor–based combinations are applicable. However, the phase 3 TALAPRO-2 trial (NCT03395197) regimen should be considered for patients harboring other mutations, such as mutations in RAD51. The regimen consists of talazoparib (Talzenna) plus enzalutamide (Xtandi), and is indicated for a broader mCRPC patient population, Gong concludes.