A range of options for metastatic castration resistant prostate cancer offer benefits, but impact on survival and sequencing guidance are less than optimal.
Recent therapeutic advances for men with metastatic castration resistant prostate cancer have yielded a range of treatment options that provide meaningful clinical benefits, according to a comprehensive review of available therapies.
Despite the large number of treatment options for metastatic castration resistant prostate cancer, the impact on survival is less than optimal and current data provide limited guidance on how to sequence approved treatments for specific patients, stated the researchers, led by E. David Crawford, MD, Department of Urologic Oncology, School of Medicine at the University of Colorado Denver in Aurora.
“Recently results from several studies of metastatic castration resistant prostate cancer began to identify clinical factors that predict benefit from androgen axis targeted and other therapies, which might help inform treatment decisions for individual patients,” the researchers noted.
They provided an overview of phase 3 trial data for androgen axis targeting agents in metastatic castration resistant prostate cancer, as well as perspectives on other recently approved metastatic castration resistant prostate cancer agents. Their review assessed the impact of resistance to agents and emerging data on prognostic factors and biomarkers.
The review noted that abiraterone and enzalutamide target the androgen axis with different mechanisms of action. Abiraterone blocks cytochrome P450 17, inhibiting androgen synthesis; enzalutamide inhibits androgen receptor, reducing nuclear translocation of the androgen receptor complex and subsequent DNA binding.
“Both agents provide improved overall survival in patients with metastatic castration resistant prostate cancer who received prior docetaxel treatment and in those who are chemotherapy naÃ¯ve,” the researchers stated.
Other agents also lead to improved overall survival in select patients. Cabazitaxel provides improved overall survival in patients with metastatic castration resistant prostate cancer with prior docetaxel therapy. Sipuleucel-T provides improved overall survival in asymptomatic patients, and 223radium provides improved overall survival in chemotherapy naÃ¯ve and chemotherapy treated patients with symptomatic bone metastases.
“Selecting the correct treatment with metastatic castration resistant prostate cancer is complex, as no head-to-head trials have been done and comparison between existing trials is difficult due to differences in study populations and a lack of validated biomarkers,” the researchers said.
Clinicians should consider certain factors, including prior therapy, symptom burden, metastasis type, performance status, comorbidities, adverse event profiles, and patient preference as well as treatment sequence because some agents affect responses to subsequent choices, they suggested. For example, resistance to abiraterone or enzalutamide may result in limited responses to subsequent androgen targeted agents.
The next challenge is to optimize treatment selection and sequencing for individual patients. “Identifying factors predictive of resistance is an area of ongoing research, with androgen receptor variants representing a good candidate,” the researchers said. “Prognostic factors for survival are also likely to be useful and are currently being studied.”
In conclusion, the researchers noted the importance of having all treatment options available, particularly in the absence of biomarkers. They stated, “It is critical to monitor the response to treatments so that the patient does not miss a valuable therapeutic window to receive alternative treatment that may prolong life.”