Metastatic non-castrate PCa: What new guideline says

Abiraterone acetate (ZYTIGA) should be considered a standard of care for newly diagnosed, metastatic, non-castrate prostate cancer, as should docetaxel (Taxotere), according to a new clinical practice guideline from the American Society of Clinical Oncology (ASCO).

When given along with androgen deprivation therapy (ADT), both abiraterone and docetaxel provide a survival benefit over ADT alone, according to the medical oncology guideline, which was published in the Journal of Clinical Oncology (April 2, 2018 [Epub ahead of print]).

The recommendations are based on an analysis of patients treated in recent randomized clinical trials that evaluated ADT with added docetaxel (GETUG-AFU 15 and CHAARTED), added abiraterone with prednisone or prednisolone (LATITUDE), or both approaches (STAMPEDE).

The strongest evidence supporting abiraterone plus ADT is in patients with high-risk de novo metastatic non-castrate prostate cancer, according to guideline authors.

Based on that finding, they said the anti-androgen therapy “should be offered” to patients with at least two high-risk features, including measurable visceral disease, three or more bone metastases, or a Gleason score of at least 8. However, they do also say the treatment “may be offered” to patients with lower-risk de novo metastatic non-castrate prostate cancer.

Likewise, the guideline says that docetaxel has its strongest evidence in men with high-volume disease, and should be offered, if a patient with high-volume disease is a candidate for chemotherapy. Again, however, they state that the treatment may be offered to patients with low-volume disease as well.

What’s not so clear at this time is whether a particular patient would benefit from one regimen more so than the other, though more data is coming, according to guideline expert panel co-chair Michael J. Morris, MD.

One effort is underway to aggregate data from randomized clinical trials to potentially tease out factors such as volume of disease, tumor characteristics, PSA kinetics, or others that may contribute to treatment benefits, said Dr. Morris, of Memorial Sloan Kettering Cancer Center, New York.

For now, there are some factors that can guide patient selection for either therapy.

“Not every patient is an optimal candidate for each. There are some patients that are really not good chemotherapy candidates; that could be based on age and co-morbidity and other factors, as well. There are other patients for whom the abiraterone is still unaffordable, and there are financial barriers that exist,” Dr. Morris said in an interview with Urology Times.

Clinicians should discuss the cost of abiraterone with patients, according to the guideline, which states that “in some health care systems it is expensive or not available to all, and treatment must be administered for the full duration of castration sensitivity.”

Next: Financial barriers may be improvingFinancial barriers may be improving, Dr. Morris said, in light of the recent FDA approval of abiraterone plus prednisone for high-risk metastatic castration-sensitive prostate cancer, inclusion in authoritative clinical practice guidelines from the National Comprehensive Cancer Network, and increasing third-party payer engagement.

Even so, the issue of choosing between abiraterone and docetaxel remains largely unresolved. The ASCO guideline notes that the two standards have not been subjected to head-to-head comparisons and have “quite similar” benefits at face value.

“There are still challenges in terms of deciding or knowing which standard of care to apply to which patient-that is, which patient with early metastatic castration-sensitive disease should get abiraterone or should get docetaxel. I think that is something that we all still are trying to work through, and we need more data to really make those decisions not based on extrapolation, but actually, evidence,” Dr. Morris said.

Dr. Morris has consulting or advisory roles with Astellas Pharma, Bayer Healthcare Pharmaceuticals, Endocye, and Advanced Accelerator Applications. Several of his co-authors have disclosures with pharmaceutical companies; for a full list of disclosures, click here.