Petrylak Discusses Significance of Genetic Testing in Prostate Cancer

Daniel Petrylak, MD

The 2017 Philadelphia Prostate Cancer International Consensus was recently held at the Sidney Kimmel Cancer Center of Thomas Jefferson University. The theme of this year’s meeting was The Role Of Genetic Testing For Inherited Prostate Cancer Risk.

“Genetics is the way of the future for patients with prostate cancer,” said steering committee co-chair Daniel Petrylak, MD.

OncLive: What are some of the key takeaways from this meeting?

In an interview with OncLive at the meeting, Petrylak, professor of Medicine and Urology, co-director, Signal Transduction Research Program, Yale School of Medicine, discussed the significance of genetics in the future of prostate cancer care and highlighted emerging treatments and challenges in the field.Petrylak: I think that prostate cancer is moving into a new era of molecularly targeted treatments and identification of DNA repair mutations in patients with metastatic prostate cancer. I think that is providing a remarkable opportunity to begin to use drugs that target these particular pathways.

For example, olaparib (Lynparza) is a PARP inhibitor and patients who are deficient in repair enzymes generally have a higher rate of response. In fact, in The New England Journal of Medicine, it was reported in a paper that 14 out of 16 patients responded in that situation, whereas a much lower percentage of patients responded if they did not have deficiencies in DNA repair.

What ongoing trials in prostate cancer are you excited about?

This is a way that we can potentially stratify patients based upon drugs, or drugs that may be effective and limit the toxicity. I think we're going to be moving forward now in prostate cancer, within the next couple of years we’ll be phenotyping everyone who has metastatic castration resistance.There are a number of trials that are focusing on DNA repair and looking at different combinations. At Yale, we are looking at exploiting hypoxia as a way of increasing potential mutation rates and then increasing sensitivity to PARP inhibitors. We have a combination trial of the VEGF inhibitor cediranib plus olaparib that is being done in all patients with metastatic disease and this can potentially make a patient who may not have been sensitive to olaparib, now sensitive.

How is the safety profile for these combinations?

What are some of the challenges the field is still currently facing that you would like to see addressed?

There were also some very exciting studies at the 2017 Genitourinary Cancers Symposium looking at combining PARP inhibitors with checkpoint inhibitors and this may increase the mutation rate and make these patients have tumors that are more visible to the immune system. I think the potential for combining these agents could make a great impact in our patients’ care.The safety profile is fairly good. These are well-tolerated drugs. Of course, with any cytotoxic agent, you are going to experience neutropenia, but overall these drugs are very well tolerated.The heterogeneity of the disease is an issue. For example, with prostate cancer, most men have the disease limited to bone. How do you obtain specimens from those patients, and are the specimens that are taken from bone similar to those from other soft-tissue lesions? Are these more predictive or less predictive? Can we develop newer circulating DNA type of assay to determine whether a patient should go on an individual drug? Regarding circulating tumor cells, can we look at these individual cells and determine whether these have mutations and again, can we target drugs for these?

What message should community oncologists take back to their practices from this conference?

I think the fact that it can be difficult to get tissue from prostate cancer patients makes us look for different ways of obtaining that liquid biopsy that may be useful in developing drugs or putting the patient on the right medication.The key takeaway is that genetics is the way of the future for patients with prostate cancer. We will start routinely testing patients when these drugs are approved by the FDA for these indications. I think that this is a very important observation for our patients and has great clinical potential.