Overall survival (OS) analysis of a phase II study using a pox viral-based vaccine, PSA-TRICOM, in the treatment of metastatic, castrate-resistant prostate cancer (mCRPC): Implications for clinical trial design.

3005 Background: Vaccine strategies represent a novel therapeutic approach for mCRPC. PSA-TRICOM is a pox viral-based vaccine that contains the transgene for PSA and 3 co-stimulatory molecules required for T-cell activation. The vaccine employs a prime/boost strategy; after an initial vaccinia-based vaccine, all subsequent vaccinations utilize a fowlpox-based vaccine. PSA-TRICOM was well tolerated in a phase I study.,32 chemotherapy naive patients (pts) with mCRPC were treated with PSA-TRICOM subcutaneously monthly with or without adjuvant GM-CSF in this phase II study with 4 cohorts. Pts were re-staged every 3 months (mos) with CT and bone scans. Elispot assay pre and post treatment was done to evaluate PSA-specific T cell response. An OS analysis has been performed on these pts; we also compared actual to predicted OS based on the Halabi Score (HS) and compared OS stratified according to T-cell responses.,On study median age=65.6 years, median Gleason Score=8 (range 6-10), median PSA=76.3, PSA doubling time=2.2 mos, HS=129. 12/32 pts (37.5%) had a PSA decline; 7 pts>20%, 5 pts>30% (max=72%). 22/32 pts lived longer than predicted by HS (p=0.05). For pts with HS>130: 10/15 lived beyond their individual predicted OS (p=0.30); 3 remain alive beyond Halabi predicted OS. For pts with HS<130: 12/17 lived beyond their OS as predicted by HS (p=0.14) with 11 pts still alive at a median follow-up of 35.8+mos. All 5 pts who had an increase in PSA specific T-cell response >6 fold remain alive 35-45+mos after enrollment compared to a median OS of 20.3 mos in pts with <6 fold response(p=0.038); 4 of these 5 pts had a HS<130.,mCRPC pts treated with PSA-TRICOM may have potential to have superior OS than predicted (p=0.05). 11/17 pts with HS<130 are alive after a median 35.8+mos follow-up and 12/17 exceed the OS predicted by HS. Furthermore, the ability of pts to mount a >6 fold increase in T-cell responses was associated with an increase in OS. These results thus provide the rationale that mCRPC pts, especially those with more indolent disease, may benefit from vaccine-mediated monotherapy; however this will need to be confirmed with larger, randomized studies. No significant financial relationships to disclose.