Abstract 643P
Background
Although Prostate Cancer Working Group (PCWG) guidelines recommend continuing treatments, such as enza, for mCRPC until radiographic/clinical progression (rPD/cPD), treatment is often discontinued using biomarkers like PSA & NaF-PET imaging.
Methods
A phase 2 trial in mCRPC randomized pts previously untreated with docetaxel, abiraterone, or enza, comparing enza +/- PROSTVAC, a therapeutic cancer vaccine, & found no difference in time to progression (PD). Most pts were followed beyond PSA rise until rPD. To determine how other biomarkers compare to rPD, we evaluated CTC count, AR-V7 status, & PD with CT/Tc99 (per PCWG) & NaF-PET (any new lesions) every 3 months (mo).
Results
57 pts (median age 67 yr & PSA 15.2 ng/mL) had a median follow up of 55.4 mo. 49/57 (86%) pts had rising PSA; median time to 1st PSA rise for all patients was 6.4 mo. 38/57 (67%) pts had PD (majority rPD; 1/38 cPD); median time to PD for all pts was 23.3 mo. In patients who experienced rPD/cPD, CTCs were detected in 11/24 (46%) samples taken at rPD vs. 3/24 (13%) samples taken at rising PSA. CTCs were higher at rPD than at rising PSA (P=0.004, Wilcoxon unpaired test). 5/11 pts were AR-V7 positive within 30 days of rPD. 18 pts underwent 182 paired Tc99 & NaF scans. Of these, 3 pts had rapid PD simultaneously on both scans, 3 pts had PD on NaF 54, 84, & 752 days prior to PD on Tc99, & 3 pts had PD on NaF at 84, 85, 261 days without PD seen on Tc99 before going off-study.
Conclusions
This data suggests that rising PSA or new lesions on PET may not be a harbinger of near-term clinically significant progression in mCRPC pts treated with enza. The 17-month difference between the 1st rise in PSA & ultimate rPD/cPD seen in this analysis demonstrates the inadequacy of rising PSA as the sole marker of PD. Furthermore, NaF scans showed new lesions before Tc99 but with unknown clinical significance given that patients had stable Tc99 scans for 54-752 days thereafter. CTCs & AR-V7 status were more associated with rPD than PSA & NaF; further analysis is pending. This affirms the need to be cautious with PSA & emerging biomarkers when assessing mCRPC pts treated with agents developed using PCWG criteria for rPD.
Clinical trial identification
NCT01867333.
Editorial acknowledgement
Legal entity responsible for the study
Ravi Madan.
Funding
National Institutes of Health.
Disclosure
A. Gill: Shareholder/Stockholder/Stock options, Full/Part-time employment: Epic Sciences. A. Tubbs: Shareholder/Stockholder/Stock options, Full/Part-time employment: Epic Sciences. J. Schonhoft: Shareholder/Stockholder/Stock options, Full/Part-time employment: Epic Sciences. All other authors have declared no conflicts of interest.