Veda Giri, MD
Genetic testing has created an impact in breast, ovarian, and prostate cancers, in terms of screening and therapeutic decisions for patients, explains Veda Giri, MD. The importance of genetics cannot only determine molecular mutations that can be targeted, but also who might be at risk for prostate cancer.
There are several mutations that have been identified and associated with prostate cancer in various studies, such as BRCA1/2
, mismatch repair deficient (dMMR) genes, and HOXB13
. A discovered mutation could lead to additional treatment options or enrollment on clinical trials that were previously not available for a patient.1
For example, if a BRCA1/2
mutation is discovered for a patient with metastatic castration-resistant prostate cancer (mCRPC), they now have the option of PARP inhibition, which has demonstrated increased survival for these patients. In 2016, the FDA granted olaparib (Lynparza) a breakthrough therapy designation for this patient population who previously received taxane-based chemotherapy and either enzalutamide (Xtandi) or abiraterone acetate (Zytiga). The phase II TOPARP-A trial demonstrated that olaparib had a nearly 90% overall response rate in a subgroup of patients who had DNA-repair defects.2
Additional PARP inhibitors are being investigated for these patients following the results demonstrated with olaparib. For instance, rucaparib (Rubraca) is being explored in the ongoing phase III TRITON3 trial versus physician’s choice of abiraterone acetate, enzalutamide, or docetaxel for patients with BRCA1/2
mutations (NCT02975934). “The development of new agents further increases the importance of genetic testing for patients with prostate cancer,” said Giri.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Prostate Cancer, Giri, an associate professor at Thomas Jefferson University Hospital, discussed the developing role of genetic testing for the screening and management of patients with prostate cancer.
OncLive: Please provide an overview of your presentation on genetic testing for patients with prostate cancer.
It is an exciting time for genetic testing and evaluation for patients with prostate cancer. The role of genetic testing for the management of screening and treatment for men is rising. In my talk, I discussed what the current management recommendations are based on genetic test results—whether it is screening, active surveillance, or emerging clinical trials for patients with metastatic prostate cancer.
It is also important to understand what it means to have genetic testing. In my discussion, I dived deeper into the current guidelines for the genes to test and which individuals might want to consider genetic testing, whether it is to help guide their treatment or to better understand their risk for prostate cancer.
I also discussed the considerations to have in mind before proceeding with genetic testing, the current implications for men and their families, and other thoughts to give to this field when proceeding with genetic testing. When is the best time for a patient to receive genetic testing and how do you know if it is appropriate? There are a few scenarios for men to consider genetic testing for inherited prostate cancer. One scenario is in the setting of a man who has had metastatic disease and has gone through the standard lines of treatment, but their disease is progressing. In that case, precision oncology is where genetics is taking off to help guide targeted therapies. Genetics can help inform additional options for treatment, such as PARP inhibitors, or help put the patient on a clinical trial for agents such as pembrolizumab (Keytruda) to target the dMMR cancers.
There are some increasing FDA indications that are emerging for PARP inhibitors and immune checkpoint inhibitors for patients with different kinds of dMMR tumors. The clinical trials that are studying PARP inhibitors and other agents, such as pembrolizumab, are growing exponentially in the space of mCRPC. That is another patient scenario where we are seeing a rise for the consideration of genetic testing.