Edwin Posadas, MD
Upfront taxane-based chemotherapy with docetaxel improved survival in patients with metastatic prostate cancer, according to phase III findings from the CHAARTED and STAMPEDE trials, but additional findings have shown strong potential with abiraterone acetate (Zytiga) as well, leading physicians to make varying therapy decisions for their patients.
In both studies, explains Edwin M. Posadas, MD, the use of first-line docetaxel in combination with hormonal treatment had a significant reduction in the risk for prostate cancer death. The field began to move quickly toward the use of docetaxel, but soon thereafter were 2 British studies—the STAMPEDE abiraterone arm and the LATITUDE study.
Both trials found that upfront use of abiraterone—an agent that was initially approved after use of docetaxel—in addition to prednisone and standard androgen-deprivation therapy (ADT), or standard initial therapy, resulted in a 38% and 37% reduction in the risk of death in LATITUDE and STAMPEDE, respectively.1,2
The only thing lacking, Posadas says, is a comparison between the studies.
“Should you give a man docetaxel or abiraterone?” he asks. “Many physicians will use their clinical judgement to make that decision. The answer probably lies in the molecular makeup of the tumor.”
As the field continues to hone in on targeted therapies in advanced prostate cancer, targeted agents like nonsteroidal antiandrogens are now being developed for patients with nonmetastatic prostate cancer, as well.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Genitourinary Cancers, Posadas discussed the evolution of prostate cancer therapy, including the earlier use of advanced-stage agents and the potential for immunotherapy in the field.
OncLive: How has systemic therapy in prostate cancer changed in the past year?
: Systemic therapy for advanced prostate cancer has really evolved in the past year. Because of the newer studies that are coming forward, what was used in the most advanced settings are now being used in earlier disease states. This is going to temporarily cause a great deal of confusion as we sort things out. It's critical at this point that physicians who are caring for men with advanced prostate cancer know what tools to use and when to use them. Old paradigms of making treatment decisions based on what line of therapy a patient has been on are probably, and thankfully, going away.
With advancements being made in molecular biology and in our understanding of the biology of advanced prostate cancers, we are entering an era with better targeting and precision of cancer care. This is incredibly important since some of the treatments are more toxic than others and have undesirable side effects—as in the commonly administered hormonally active agents that we use. In the right setting at the right time, we're finding that it really makes a difference in a patient’s quality of life. I’m very excited to be involved in work at this point in time in prostate cancer.
Can you speak to how the CHAARTED, LATITIUDE, and STAMPEDE trials are affecting sequencing strategies?
There have been 3 very large and powerful studies that were put forward within the past 3 years. LATITUDE and STAMPEDE were shown at the 2017 ASCO Annual Meeting. Prior to those studies were the CHAARTED and STAMPEDE docetaxel-focused studies. CHAARTED and STAMPEDE showed that upfront taxane-based chemotherapy, also known as hormonal therapy, improved survival. This is a landmark finding and has resulted in a paradigm shift.
Chemotherapy is generally reserved until the very end because of the perception patients and physicians have that it is toxic and has undesirable side effects. While generally this is true, chemotherapy for prostate cancer is somewhat milder than it is for other neoplasms. Using it at the right time is really important.
What has complicated this even further is the data presented by Drs Maha Hussain of Northwestern University Feinberg School of Medicine and Eric Small of University of California, San Francisco at the 2018 Genitourinary Cancers Symposium. Hussein and Small presented the results from the PROSPER and SPARTAN studies. These trials looked at 2 other agents, enzalutamide (Xtandi) and apalutamide (Erleada), other androgen receptor (AR)-blocking agents or nonsteroidal antiandrogens. These are being used by many clinicians in the nonmetastatic castration-resistant prostate cancer (CRPC) space. After castration, men with a rising prostate-specific antigen (PSA) will receive ADT in the absence of detectable metastatic disease.