Leonard G. Gomella, MD
The year ahead in the prostate cancer paradigm is expected to include an increased use of genetic testing, approximately 2 more FDA approvals, a debate between agents in the nonmetastatic castration-resistant setting, and a reversed opinion on screening, explains Leonard G. Gomella, MD.
2018 began with the FDA approval of apalutamide (Erleada) in February for patients with nonmetastatic castration-resistant prostate cancer (CRPC), which is the first FDA-approved therapy in this setting. In March, the agency granted a priority review designation to a supplemental new drug application for enzalutamide (Xtandi) in the same population. If approved, Gomella predicts the decision on which agent to use first will spark a debate within the community.
“We started the year with apalutamide, but there are going to be at least 2 or 3 more [drugs] that will be added to our ability to care for men with advanced prostate cancer,” said Gomella, professor, chair, Department of Urology, director, Sidney Kimmel Cancer Center Network, Thomas Jefferson University Hospital.
In addition, he says, PARP inhibitors are also being investigated for patients with metastatic castration-resistant prostate cancer (mCRPC). But systemic therapy advances aside, Gomella stresses that genetic testing and prostate cancer screening will also be major topics of discussion in the field.
In an interview during the 2018 OncLive® State of the Science Summit™ on Prostate Cancer, Gomella, who also co-chaired the meeting, shared his insight on the expected transformations in the field of prostate cancer.
OncLive: What are some of the advancements across the field of prostate cancer that were discussed at the meeting?
We spoke about a variety of areas from early disease to late disease, and we touched upon some of the new areas, which include the issues about genetic testing for prostate cancer. This has certainly been very common in breast cancer, but not so common in prostate cancer. We also spoke about the latest developments in the new approval of medications, such as apalutamide for patients with M0 CRPC, and tried to take every one of the major developments that was at the 2018 Genitourinary Cancers Symposium and bring it to the local audience in Philadelphia.
How widespread is genetic testing in prostate cancer?
The current status of screening for prostate cancer is, really, at a very low level. We are actually learning more and more about it; we have only recently had NCCN guidelines that begin to recommend which patients should have genetic testing for potentially inherited prostate cancer risk. However, one of the things we really have to get out to individuals and providers that care for men with prostate cancer is that when you [report] family history, don’t just focus on prostate cancer. [Focus on] breast cancer, ovarian cancer, melanoma, pancreatic cancer, Lynch syndrome, gastrointestinal tract tumors, [and] upper tract urothelial tumors, which all may be related to inherited risk for prostate cancer.
Now, we don’t know exactly how many men have clearly inherited prostate cancer risk. We know the number is high, but [we don’t know] exactly what that number is right now—we are identifying the men who have the factors that contribute to prostate cancer and put [them] at increased risk. It doesn’t necessarily mean you’re going to get prostate cancer, but it puts you at a heightened risk. You should consider [perhaps] early screening or a different approach in an individual who may have one of these inherited prostate cancer risk factors.
Are there any biomarker-driven clinical trials designed to figure this out?
The status of trials right now in the United States are not as robust as they are in Europe and in England, where they are doing very focused screening on patients who identify as either having an individual BRCA1/2 abnormality or where it’s in the family.
Right now, in the United States, we are finding our way. A lot of the commercial companies are presenting us with these multigene panels that cover a lot of different genes. Again, we are just not at the point yet where we can make broad-based recommendations for genetic screening. We recommend, and strongly feel, that genetic counselors should be involved in these discussions. This is particularly for patients who come in with 2 or 3 members of the family with high-grade prostate cancer, or a couple family members with high-grade prostate cancer and maybe a sister or mother with breast or ovarian cancer. We think that those people should first be referred to a genetic counselor to decide [whether] there [is] apparently enough risk in that individual to warrant further genetic testing.
This is because genetic testing can be very complicated, and there are a lot of issues with genetic testing that people need to be aware of, concerning things such as life insurance. You can’t be discriminated against by an employer, but there are things such as disability and life insurance that might be impacted. Therefore, we have to be a little bit cautious in this very early phase that we are currently in of understanding inherited prostate cancer risk.
Let’s transition to apalutamide. What is the significance of this approval and its recent incorporation into the NCCN guidelines?
Apalutamide was a big breakthrough for us because we had so many men who would have slowly rising prostate-specific antigens (PSAs) with no evidence of metastatic disease, that we sort of sat back and didn’t do too much with. To be fair, not all men with slowly rising PSAs without evidence of metastatic disease who are castrated already are going to progress rapidly. This is really for those patients who have very high doubling times and we are worried about them progressing to metastatic disease. [Apalutamide] does delay the development of metastatic disease significantly.
What do you expect to be achieved this year in prostate cancer?
This year, we are going to have a few more drug approvals. In particular where we suspect, based on both the PROSPER and the SPARTAN trial, that enzalutamide may be approved in the same space that we just had apalutamide approved for in the M0 CRPC space.
The PARP inhibitors are on the fast track this year to be used as another agent for mCRPC. What is going to be interesting about that is that [the approval(s)] will be connected to a biomarker. Again, this is BRCA1/2, [but there are] other genes that we are just getting into the lingo of urology in urologic oncology. We are going to have several major drug approvals that will continue.
If enzalutamide gets approved in the nonmetastatic CRPC setting, will we run into a debate of which agent to use first?
The debate of whether to use apalutamide or enzalutamide is going to be a repeat of the abiraterone acetate (Zytiga)/enzalutamide debate. Again, it will occupy a lot of peoples’ time figuring out which agent may be better in individual patients. There are subtle differences in the side effect profile that may impact one drug over the other as a choice. But again, when you see the SPARTAN and PROSPER trials, it’s kind of “deja vu all over again” with the enzalutamide and abiraterone debate.
What is one of the key challenges remaining in prostate cancer?
The biggest thing that we are also going to hear about this year doesn’t have to do with any approvals, but it’s going to be the US Preventative Services Task Force, which is acknowledging that some people may benefit from screening for prostate cancer. In 2012 [the group] basically said, “You should not test anyone. You should not screen an asymptomatic man for prostate cancer.”
Last year, they came out with a draft statement for public comment that, in men under the age of 70, there may be a benefit [to screening] and [physicians] should have dialogue with their patients about it. We haven’t seen that formal publication yet, but it should be coming soon. That will be a change in the perception of the risk and benefit of screening for prostate cancer that will be impacted in the coming year. We are concerned that we are seeing slightly increased rates of patients with node positivity and then presenting with metastatic disease. It is debated, but there is something clearly going on in the last 3 or 4 years that seems to be reversing a trend of decreasing the diagnosis of men with advanced disease.