Bradley A. McGregor, MD, sheds light on recently approved agents, as well as a multitude of novel therapies on the horizon, that appear to spell out a promising future for the treatment of patients with nonmetastatic castration-resistant prostate cancer.
Bradley A. McGregor, MD
Recently approved agents, as well as a multitude of novel therapies on the horizon, appear to spell out a promising future for the treatment of patients with nonmetastatic castration-resistant prostate cancer (CRPC) and hormone-sensitive prostate cancer (HSPC), said Bradley A. McGregor, MD.
“From my standpoint, therapies continue to evolve in prostate cancer,” said McGregor. “Independent of the space, the treatments that we used to think of in later-line settings are being used earlier, including in the nonmetastatic CRPC setting and up-front HSPC setting. Beyond that, we still need to continue to look for novel approaches and learn how we want to adapt novel imaging into [practice].”
However, despite the rapidly evolving and expanding field, the coronavirus disease 2019 (COVID-19) pandemic presents specific challenges in the field, including the ultimate question of whether to delay therapy.
In an interview with OncLive® during the 2020 Institutional Perspectives in Cancer (IPC) webinar on Genitourinary (GU) Malignancies, McGregor, clinical director of the Lank Center for Genitourinary Oncology, a senior physician at Dana-Farber Cancer Institute, and an instructor of medicine at Harvard Medical School, discussed the current treatment paradigm of prostate cancer, specific obstacles that are being faced as a result of the COVID-19 pandemic, and future research efforts aimed at mitigating ongoing challenges in the space.
OncLive®: What does the current treatment paradigm of prostate cancer look like, and what are the most exciting recent updates to happen in this space?
McGregor: In prostate cancer, we’ve had a lot of developments on several fronts over the past several years. One of the things that we discussed quite a bit was the advances in nonmetastatic CRPC in those situations where we don’t have evidence [of disease] by conventional imaging, but the patient’s prostate-specific antigen (PSA) is rising despite having captured levels of testosterone. Now, we’ve had multiple trials showing an improvement in overall survival (OS) with more intense [antiandrogens] such as enzalutamide (Xtandi), darolutamide (Nubeqa), and apalutamide (Erleada). Certainly, these are very exciting data from that standpoint.
Another question that was brought up is how do we define nonmetastatic? As we get new imaging with fluciclovine 18 (Axumin) PET and, hopefully, PSMA PET in the future, what is considered nonmetastatic by conventional imaging will not be considered nonmetastatic in the future. Learning how to integrate these drugs into that space will be something we need to continue to evaluate.
One of the other major advances has been incorporating those same drugs into the up-front setting of metastatic prostate cancer. Traditionally, the up-front standard of care for men with HSPC has been androgen deprivation therapy (ADT). Then we had the CHAARTED trial which showed that the addition of docetaxel specifically in patients with a high volume of disease led to a marked improvement in overall survival (OS). Now, we have data showing that we can get the same benefit with further [antiandrogen therapy, so] abiraterone acetate (Zytiga), enzalutamide, and apalutamide have all been proven in that space.
What is your viewpoint on the COVID-19 pandemic, and how has it affected the treatment of patients with prostate cancer?
One of the key things about this is that just because COVID-19 is happening, that doesn’t mean cancer ceases to exist. We still need to offer our patients effective therapy when possible. What therapies need to be offered can vary based on the disease state. So, if you have someone who has a Gleason [score of] 6, as would be the case outside of COVID-19, surveillance is the preferred approach. However, if you have someone who has a Gleason [score of] 3+4, or 4+3, that situation may merit definitive therapy, but it is OK to delay [treatment] by 3 or 4 months. Any patients who have high-risk disease [or] a Gleason score of 8 or 9, need to undergo definitive therapy earlier rather than later. It is those situations where up-front surgery makes sense if patients are candidates. Trials, such as the PROTEUS study, are looking at the role of perioperative ADT, which is certainly appealing in that situation. Six months of ADT could allow you to defer surgery hopefully to a point where there is more availability and a lower risk from a COVID-19 standpoint.
Based on your experiences at Dana-Farber Cancer Institute, what are some of the strategies that have been employed to mitigate some of the challenges faced during the COVID-19 pandemic?
As a group, we met to come up with some clinical guidelines to help guide us through COVID-19. We looked across the diseases we treat, including prostate cancer, renal cell carcinoma, bladder cancer, and testicular cancer.
At the end of the day, the goals of those therapies are not to delay or defer necessary therapy, but to use therapy judiciously. When multiple therapy options are available, choose the one with the least risk for infectious complications or need for high-dose steroids. Attempt to minimize visits to minimize exposure risks.
In terms of ongoing clinical trials and research efforts, what challenges has COVID-19 posed?
When you look at clinical trials, it has been challenging with COVID-19. It doesn’t just affect the clinic operations, but it affects research operations as well. A lot of things go on behind the scenes with research coordinators, tissue acquisition in labs, and things that may not be feasible during a pandemic.
[Interventional radiation] wasn’t offering biopsies for a period of time for research purposes or wasn’t able to get tissue processed. Certainly, research has been more challenging, but it hasn’t stopped in that we continue to provide care for our patients. If there is a clinical trial where the risk/benefit ratio continues to be acceptable even in the face of COVID-19, that is something we will continue to pursue.
Prior to COVID-19, what challenges had arisen in the prostate cancer space?
We have a lot of different drugs [available] in prostate cancer. One of the challenges is trying to figure out whether there is a right order [to give these therapies in]. Right now, we have a lot of drugs that can be used in the same space, but if that doesn't work, what are our next options? It’s great; we are moving a lot of therapies that we know work well into earlier [lines of treatment]. However, we are unfortunately still left with a lack of options later on.
It is now pretty clear that if you start on therapy and progress quickly that cabazitaxel (Jevtana) is reasonable based on the CARD trial. Now we have the approval of PARP inhibitors, as well. However, we still need to continue to do better for our patients. There are ongoing trials with immunotherapy, cabozantinib (Cabometyx), and different PARP inhibitors, looking at ways to try to maximize therapeutic efficacy in the later-line settings.
What other emerging therapies are on the horizon that look particularly promising?
Overall, things that we are looking forward to in prostate cancer [treatment] going forward are going to be novel imaging with the hope that in using PSA PET, we may find [that treating] oligometastatic disease with aggressive local therapies delays the need for prolonged systemic therapy. Obviously, we’ve seen some great therapies with PARP inhibitors that are now approved for those patients. I think immunotherapy is very exciting, although it hasn’t been as exciting in prostate cancer to date. Although, we have seen phase 1 data for the combination of cabozantinib and atezolizumab (Tecentriq), showing pretty impressive responses in those patients who had failed abiraterone or enzalutamide in the CRPC setting. I’m excited for those developments in the ongoing phase 2 trial.