Progression-Free Survival versus Overall Survival in Patients with PSA-Recurrent Prostate Cancer: Long-Term Analysis of a Randomized Phase 2 Trial of pTVG-HP versus Placebo.

Background: We previously reported results from a randomized phase 2 trial evaluating a DNA vaccine (pTVG-HP) versus placebo (GM-CSF vaccine adjuvant alone) in patients with PSA-recurrent, nonmetastatic, non-castrate prostate cancer (NCT01341652). The primary endpoint of 2-year metastasis-free survival (MFS) was not different between the treatment arms. This trial was reopened for long-term evaluation at one study site. Methods and Results: The median follow-up for long-term overall survival was 4.1 years (range 0.1-13.8+ years). Median overall survival of 48 patients treated with pTVG-HP was 13.4 years versus 8.6 years for 49 patients treated with placebo (log-rank test p-value=0.020). Long-term follow-up information on survival and subsequent treatments was available for 59 patients. Of these, 56 were treated with subsequent androgen deprivation therapy (ADT). When analyzing overall survival for this cohort, the adjusted hazard ratio was 0.56 (p=0.021) when comparing pTVG-HP vs. placebo, after adjusting for ADT and subsequent treatment exposure. The median time to beginning ADT was 2.2 years for patients randomized to pTVG-HP versus 1.4 years for patients randomized to placebo (p=0.192). The median time to the next therapy for castration-resistant disease after beginning ADT was 4.7 years for patients randomized to pTVG-HP versus 2.1 years for patients randomized to placebo (p=0.112). Conclusions: These results suggest that pTVG-HP may have had single-agent benefit that could not be appreciated using a MFS endpoint, challenging the notion that MFS can uniformly serve as a surrogate endpoint for overall survival in this stage of disease.