Hitting New Targets in Metastatic Prostate Cancer

In season 4, episode 3 of Targeted Talks, Pedro Barata, MD, MSc, director, Clinical Genitourinary Medical Oncology Research Program, UH Seidman Cancer Center, and associate professor of Medicine, Section of Hematology and Medical Oncology at Case Western University, discusses the present and future of metastatic prostate cancer precision medicine.

Barata explains that molecular profiling provides helpful information for treatment decision and to assess how patients will respond to targeted therapy. For example, Barata says that 2%-3% of prostate cancers have microsatellite instability or high tumor mutational burden, and these tumors are known to be responsive to immune checkpoint inhibitors. In other cases, homologous recombination deficient tumors are known to respond to PARP inhibitors. There are many other biomarkers, Barata notes, including PSMA.

“We have other kind of biomarkers. I'm thinking of the expression of PSMA, and the use of a PSMA-based therapy such as lutetium PSMA. Or we can even have this kind of alteration genes, for example, TP53, RB1, p10, where you basically define molecularly, this aggressive variant, prostate cancer. For instance, there's data suggesting that for those patients, a combination of a chemotherapy regimen seems to be better than cabazitaxel [Jevtana] alone. With the emergence of molecular profiling, I think we are learning a lot more,” Barata says.

In terms of available treatment for these targets, Barata explains that immunotherapies have a disappointing response rate of around 10%. However, targeted therapies continue to show promise. The examples Barata give include PARP inhibitor therapy, PSMA-targeted therapy, and BiTE therapy.

The unanswered questions surrounding treatment of metastatic prostate cancer include how to sequence the available therapies, how to better predict response to therapy, and the future of immunotherapy. Additional challenges exist in the field, explains Barata.

“We can’t cure the vast majority of patients who present with metastatic prostate cancer. So, the goal then is to control the disease. So, once patients become castration-resistant, the number of treatments we use, unfortunately, are not able to provide as durable remissions,” he says.

Another issue in this space is racial disparity, which disproportional affect African American males, Barata explains. Although this group has been shown to response the same to systemic therapies as patients of other races, the is limited access to care and their diseases are caught in the later stages. Barata says there need to be collaboration in the field to address this issue.

Looking forward, studies focusing on things like PARP inhibition and treatment based on homologous recombination status have the potential to be practice-changing, according to Barata.