‘More Is Not Better’ in Metastatic Castration-Resistant Prostate Cancer


This study compared combination therapy with enzalutamide, abiraterone, and prednisone vs enzalutamide alone in men with metastatic castration-resistant prostate cancer.

CHICAGO-Combination therapy with enzalutamide, abiraterone, and prednisone did not prolong overall survival in men with metastatic castration-resistant prostate cancer (CRPC) compared with enzalutamide alone.

The results of the Alliance A031201 study (abstract 5008) were presented by Michael J. Morris, MD, of Memorial Sloan Kettering Cancer Center in New York, at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.

When androgen receptor agonists are used for the treatment of metastatic CRPC, compensatory mechanisms can limit the anti-androgen activity. Therefore, the Alliance A031201 investigators hypothesized that combining the anti-androgen enzalutamide with the androgen biosynthesis inhibitor abiraterone to prevent androgen compensation would prolong survival. The primary endpoint was overall survival (OS).

“Secondarily, this was the third of a preplanned series of prospective studies to qualify radiographic progression–free survival (rPFS) as a regulatory outcome measure sufficient for new drug approval and, therefore, we examined the relationship of rPFS and OS,” said Morris.

The phase III trial included patients with progressive metastatic CRPC who had not received prior treatment with taxanes or enzalutamide, abiraterone, and prednisone; however, chemotherapy was allowed for nonmetastatic prostate cancer that had progressed. In total, 1,311 patients were randomized to receive enzalutamide (n = 657) or enzalutamide plus abiraterone and prednisone (n = 654). Randomization was stratified by prior chemotherapy and Halabi prognostic three risk groups, factors which were adjusted for in the primary analysis.

Of the 1,311 patients, 15.6% were high risk, 35.3% were intermediate risk, and 48.1% were low risk. The median OS was 33.6 months (95% CI, 30.5–36.4 months) for the enzalutamide group and 32.7 months (95% CI, 29.9–35.4 months) for the enzalutamide/abiraterone/prednisone group (P = .53). A 50% decline rate in prostate-specific antigen levels was 80% for patients on enzalutamide plus abiraterone and prednisone and 76.5% for those taking enzalutamide alone. 

“There’s simply not that much more anticancer activity in one arm vs another,” said Morris.

The investigators continued to image the patients post-treatment if the patients ended treatment for nonradiographic progression–related reasons, providing on-treatment and off-treatment rPFS. Overall, rPFS was not different between the on- and off-treatment groups; however, to qualify rPFS as a regulatory biomarker for drug approval, the correlation between on-treatment rPFS and OS (Kendall’s tau), which represents a per-patient level analysis, was strong, at 0.70 (95% CI, 0.67–0.72), meaning that “the faster a patient progresses, the shorter his life,” noted Morris.

Progression or death occurred in 48% of patients taking enzalutamide/abiraterone/prednisone and 57% of patients taking enzalutamide alone. The primary reason for discontinuing treatment was radiographic progression (enzalutamide, 42% vs combination, 33%).

Grade 3–5 adverse events occurred in 55.6% and 68.8% of patients taking enzalutamide and enzalutamide/abiraterone/prednisone, respectively. Treatment discontinuation (12% vs 5%) and patient withdrawal rates (13% vs 5%) were higher in the combination group due to adverse events.

“The Alliance study shows that more is not better in first-line metastatic therapy,” said Michael Carducci, MD, of the Sidney Kimmel Cancer Center at Johns Hopkins, who was the discussant for the study.

Related Videos
Anemia in patients who receive talazoparib plus enzalutamide for metastatic castration-resistant prostate cancer appears to be manageable without any compromises in patient-reported outcomes and quality of life.
Artificial intelligence models may be “seamlessly incorporated” into clinical workflow in the management of prostate cancer, says Eric Li, MD.
Robust genetic testing guidelines in the prostate cancer space must be supported by strong clinical research before they can be properly implemented, says William J. Catalona, MD.
Financial constraints and a lack of education among some patients and providers must be addressed to improve the real-world use of certain prostate cancer therapies, says Neeraj Agarwal, MD.
Novel anti-PSMA monoclonal antibody rosopatamab is capable of carrying a bigger payload of radiation particles, which may potentially reduce doses for patients with prostate cancer, says Neeraj Agarwal, MD.
Findings from recent studies support the use of artificial intelligence-based tools in the context of radiation therapy for patients with localized prostate cancer, according to Neeraj Agarwal, MD.
Germline testing may elucidate important mutations in patients with metastatic prostate cancer who may be eligible to receive treatment with PARP inhibitors, according to Neeraj Agarwal, MD.
In this September edition of Snap Recap, we share our highlights from Prostate Cancer Awareness Month, news in the breast cancer space, and the latest FDA updates.
Artificial intelligence programs may help introduce new care strategies that minimize the risk of adverse effects in patients with prostate cancer, according to Wayne G. Brisbane, MD.
Related Content