Since we have many new treatments for men with castrate resistant metastatic prostate cancer (mCRPC) (advanced prostate cancer) we need to develop earlier indicators of when a treatment might or might not be successful. A decline in prostate-specific antigen (PSA) is widely used to monitor treatment response, but it has not been validated as an endpoint for the very important goal, overall survival (OS).
Abiraterone Acetate (Zytiga)(AA) is one of these newer treatments that we need to explore and understand when to switch or continue on with the drug . Solid metrics will help guide good clinical decision making.
To evaluate the actual association between an early PSA decline and overall survival (OS) following abiraterone acetate (AA) treatment researchers identified mCRPC men treated with AA before or after docetaxel at the Royal Marsden NHS Foundation Trust between 2006 and 2014.
They defined early PSA decline as a 30% decrease in PSA after 4 weeks of treatment relative to baseline, and an early PSA rise as a 25% increase over baseline. They then analyzed the association with OS and PSA changes at 4 weeks and 12 weeks.
They evaluated 274 men. A 30% PSA decline at 4 weeks was associated with longer OS and a 25% PSA rise at 4 weeks with shorter OS
The percentage PSA decline at 4 weeks was significantly correlated with the percentage PSA change at 12 weeks, the time period many clinicians like to wait prior to evaluating a treatment’s efficacy. The men who achieved a 30% PSA decline at 4 weeks were 11.7 times more likely to achieve a 50% PSA decrease at 12 weeks as well as an increase in their OS.
Keep in mind that this study does have the built in limitation that it is designed as a retrospective analysis.
Men not achieving 30% PSA decline after 4 weeks of AA have a lower likelihood of achieving PSA response at 12 weeks and significantly inferior OS. Currently many clinicians recommend waiting 12 weeks before making treatment changes, this study suggests that early PSA changes are associated with survival in patients receiving abiraterone acetate and that clinicans might wish to make efficacy determinations at 4 weeks instead of 12 weeks.
European urology. 2016 Mar 07 [Epub ahead of print], Pasquale Rescigno, David Lorente, Diletta Bianchini, Roberta Ferraldeschi, Michael P Kolinsky, Spyridon Sideris, Zafeiris Zafeiriou, Semini Sumanasuriya, Alan D Smith, Niven Mehra, Anuradha Jayaram, Raquel Perez-Lopez, Joaquin Mateo, Chris Parker, David P Dearnaley, Nina Tunariu, Alison Reid, Gerhardt Attard, Johann S de Bono