Recent results from the phase III CHAARTED, STAMPEDE, and LATITUDE trials have highlighted various strategies for optimizing androgen-deprivation therapy (ADT) in patients with advanced or metastatic prostate cancer.
“The field has shifted away from a one-size-fits-all approach for ADT to one that is really adapted toward a patient’s disease state,” explained Rahul Aggarwal, MD.
In an interview during the 2017 OncLive®
State of the Science SummitTM on Genitourinary Cancers, Aggarwal, assistant professor, director of the STAND Clinic, Helen Diller Family Comprehensive Cancer Center at University of California, San Francisco (UCSF), discussed maximizing ADT in prostate cancer. In his presentation during the meeting, he also highlighted the success of recent studies of ADT, as well as its future utilization in various stages of disease.
OncLive: Can you provide an overview of your lecture on ADT?
I spoke about ADT for patients with prostate cancer, and, in particular, I focused on some of the recent data that have come out with the use of abiraterone acetate (Zytiga) and some of the new potent androgen receptor (AR)-targeting therapies and how they have really changed practice patterns—especially for patients with metastatic prostate cancer. I focused on those studies and how to apply them in practice.
I did discuss the difference between the LHRH antagonists versus the agonists, the choice of ADT, and what the current data and practice patterns are. I also shed light on the emerging clinical trials looking at earlier use of even more potent therapies—not just in the metastatic setting, but in the earlier disease settings by a chemical recurrence—and localized prostate cancer.
What are some of the most significant data that we have now?
There have been 2 hallmark studies that were presented earlier this year looking at the use of abiraterone in conjunction with standard ADT for patients with metastatic prostate cancer. One trial is the LATITUDE study, which is a Janssen-sponsored, randomized, phase III study that looked at abiraterone plus ADT versus ADT in patients who have metastatic prostate cancer with high-risk features—3 or more metastases or higher Gleason grade. It showed a pretty convincing overall survival benefit with the combination compared with standard ADT.
Those data were supported by a second phase III study that was also reported at the 2017 ASCO Annual Meeting. That was an analysis from the STAMPEDE study, which is a large United Kingdom-run study with multiple arms—a sort of adaptive clinical trial design. One of the comparisons that they did was adding abiraterone to ADT versus ADT monotherapy—a very similar design [to LATITUDE]. This study was a little bit more inclusive, as it had a lot of different patient groups—those with high-risk localized cancer, those with node-positive disease, and patients with metastatic cancer. Therefore, it was a little bit broader of a group, but the overall outcomes—particularly in metastatic patients—was similar to LATITUDE, and we see a pretty convincing survival benefit there.
For the patients with newly diagnosed metastatic prostate cancer, the standard of care has really shifted toward more intensive therapy. There is still an open question in the field about previous data from CHAARTED and other studies that suggest adding docetaxel to ADT also achieves improvement in long-term survival in these patients. There is still an open question about which agent to choose and whether we can combine them.
Can you discuss the differences between agonists and antagonists?
We have a study that we are doing in biochemical recurrence that is being run through the Alliance Foundation Trials, in which we are using degarelix (Firmagon)—an LHRH antagonist—as the standard ADT backbone in all 3 arms. That study is degarelix alone, degarelix plus apalutamide, and degarelix plus apalutamide and abiraterone—so it’s sort of throwing the kitchen sink at these patients but treating for a finite period of time. We treat for 12 months and then we stop. What we are really aiming for is whether we achieve long-term progression-free survival (PFS) or perhaps even cure some of these patients with biochemical recurrence, which we didn’t think was feasible with ADT alone.