David R. Wise, MD, PhDD
2018 may be the year that checkpoint inhibition breaks through in the treatment landscape of prostate cancer, according to David R. Wise, MD, PhD.
Currently, the only immunotherapy approved specifically for the treatment of patients with prostate cancer is sipuleucel-T (Provenge); however, checkpoint inhibitors, such as pembrolizumab (Keytruda), are showing promise in the castration-resistant setting.
Beyond immunotherapy, PARP inhibitors are also showing promise as investigators continue to understand the genetic implications of the BRCA1/2
gene beyond its significance in breast and ovarian cancer. Not only are these 2 types of therapy showing early efficacy as single agents, but they are beginning to be investigated in combination, as well.
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Genitourinary Cancers, Wise, an assistant professor at NYU Langone’s Perlmutter Cancer Center, discussed the promise for immunotherapy and other emerging approaches in the field of prostate cancer.
OncLive: Can you please provide an overview of your presentation?
: I gave an overview of some of the newer approaches for prostate cancer treatment. I covered some of the recent advancements in novel androgen receptor (AR)-directed therapies for use in advanced prostate cancer, with the theme of "earlier is better.” Using our more effective and very well-tolerated therapeutics in patients who present with newly diagnosed metastatic non–castration-resistant prostate cancer has dramatically improved outcomes, and our patients are already benefitting from them. We took more of a granular look at those studies and analyzed some of the limitations, but also some of the nice results and how to apply them in the current clinical setting.
I also spoke about some newer advances in terms of precision oncology, how we are looking at the specific genetic features of our patients' cancers and using those to guide our clinical trial design and decision making. Hopefully, this will soon include actual clinical decision-making with the use of FDA-approved agents.
I ended with some of the things that are on the horizon in terms of bringing immunotherapy into prostate cancer. Many have been waiting for those advances that have been so exciting in other cancer types to make their way into prostate cancer practice.
In terms of AR-directed therapy, what are some of these recent advances?
What created a lot of buzz at the [2017 ASCO Annual Meeting] was the use of abiraterone acetate (Zytiga) with prednisone. We know it’s an approved agent for patients with metastatic castration-resistant prostate cancer (mCRPC), whether pre- or post-chemotherapy; however, what wasn't clear was whether the use of it in patients who were newly diagnosed or recurrent with non–castration-resistant prostate cancer with high-risk features would be beneficial. That is what we are looking into a bit closer tonight—these 2 presentations made at the 2017 ASCO Annual Meeting of the LATITUDE and STAMPEDE trials, and the outcomes and potential limitations of these studies.
Apalutamide has been granted priority review status for nonmetastatic CRPC. If that agent is approved, what potential impact could it have?
It will shift the landscape. We do see patients with nonmetastatic CRPC; some would term it rising prostate-specific antigen (PSA) that is castration-resistant. I would speculate that apalutamide will become an important treatment option for those patients who are high-risk, as those with castration-resistant disease are, even if their disease is not metastatic. We will see that included in our armamentarium that we have available to us, and other trials are going to be reported soon in that nonmetastatic context with enzalutamide (Xtandi) and darolutamide (ODM-201). That is a pretty crowded space with some therapeutics that are generally well tolerated, so there is a lot of interest and enthusiasm about that.
Are there any current clinical trials that are showcasing examples of precision medicine?
We are excited about this on several fronts. At NYU Langone’s Perlmutter Cancer Center, we have several trials that are investigating precision oncology hypotheses directed at the main genetic features of cancer that we are seeing in our patients. One involves the cancers that have DNA-repair defects, and those are cancers that have BRCA1/2
and are better known for causing hereditary breast and ovarian cancer. However, what is less appreciated is that men are affected by these mutations, as well. First-degree male relatives of female carriers of the BRCA1/2
gene are at risk and should undergo genetic testing. The flip side of that is we have found that those genetic features to be quite sensitive to a newer class of compounds called PARP inhibitors in earlier-phase studies.