Evan Ya-Wen Yu, MD
The CHAARTED, STAMPEDE, and LATITUDE trials have manifested in a dramatic clinical benefit for patients with metastatic castration-naïve prostate cancer, explained Evan Y. Yu, MD, enabling physicians to turn their attention toward those with oligometastatic disease, earlier detection, and the potential for metastatic therapy.
In the phase III LATITUDE trial, the addition of abiraterone acetate (Zytiga) and prednisone to standard androgen deprivation therapy (ADT) resulted in a 38% reduction in the risk of death versus ADT alone.1
The findings served as the basis for the February 2018 FDA approval of abiraterone for patients with metastatic high-risk castration-sensitive disease.
The STAMPEDE trial further investigated the use of abiraterone in this patient subset and demonstrated a 37% reduction in the relative risk of death when added to standard ADT in patients with high-risk hormone-naïve prostate cancer.2
The CHAARTED trial took patients with metastatic hormone-sensitive prostate cancer and randomized them to receive either ADT plus docetaxel or ADT alone. At a median follow-up of 53.7 months, overall survival (OS) results revealed a median OS of 57.6 months versus 47.2 months with the combination of docetaxel and ADT and ADT, respectively.3
“What I tend to do is take patients who have high-volume metastatic disease and offer them either docetaxel or abiraterone [after accounting for] comorbidities, side effects, cost issues, and practicality issues,” said Yu. “About half of my patients opt for docetaxel and half opt for abiraterone. For patients with low-volume disease, I feel the data are stronger and I offer them abiraterone.”
Considering the recent success in the metastatic space, Yu explained that the next wave of research will focus on earlier detection and intervention for those with oligometastatic and low-volume disease.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Genitourinary Cancers, Yu, a professor in the Department of Medicine, Division of Oncology, University of Washington, Seattle Cancer Care Alliance, discussed the available options for patients with metastatic castration-naïve prostate cancer.
OncLive: What are the current therapies used in patients with metastatic castration-naïve prostate cancer?
: Metastatic castration-naïve prostate cancer is a disease state we're seeing more and more of as time goes on, partially because there's less prostate-specific antigen (PSA) screening. As a result of that, we're seeing patients with an unmet need. Recently, there have been quite a bit of exciting data looking at adding therapies to standard ADT. We've seen that docetaxel has led to a dramatic survival benefit when added to ADT in both the CHAARTED and STAMPEDE trials. When added to ADT, abiraterone with prednisone also [results in] a dramatic survival benefit, as seen in LATITUDE and in an arm in STAMPEDE.
This leads to a little bit of a clinical dilemma, in which one asks whether we should use docetaxel or abiraterone. At this point in time, a few things are clear. For high-volume or high-risk metastatic disease, patients gain a survival benefit from docetaxel; that’s not clear for patients with low-volume disease. In the CHAARTED trial, high-volume was defined as 4 or more bone metastases with at least 1 outside the axial skeleton or visceral lesions.
At the same time, there are clear data from the LATITUDE trial, which showed that patients with high-volume disease as well as high-risk patients have a survival benefit from abiraterone. High risk was defined as 2 of 3 criteria: either a Gleason score of 8 or greater, 3 or more bone metastases, or visceral lesions. Posthoc analyses presented at the 2018 ESMO Congress showed a clear survival benefit with abiraterone in patients with low-volume or low-risk disease.
Now, the next step is to evaluate the new data on oligometastatic treatment. We already have data in colon cancer and other cancers, such as lung cancer, but the data are unclear in prostate cancer. [However], trials are ongoing, and some of them are also looking at eradicating the primary lesion of the prostate. Theoretically, there's a rationale for this, because the primary will shed lesions—micrometastases—that will set down and create more metastases. Ablating those [metastases] at a lower-volume disease state might be ideal. With that being said, there are studies reading out [that are evaluating] ablation of the primary prostate lesion of a patient with metastatic disease.
The HORRAD trial was negative for those with high-volume disease or those with a high prostate-specific antigen (PSA) greater than 20. The median PSA was in the 50s. With that being said, there was an arm in the STAMPEDE trial where patients were given lower doses of radiation, such as 55 Gy over 4 weeks to the prostate.