No delay in progressive CSPC metastasis with PAP-targeted vaccine
medwireNews: Phase II study data suggest that the prostatic acid phosphatase (PAP)-encoding pTVG-HP vaccine does not improve metastasis-free survival (MFS) in men with progressive, nonmetastatic, castration-sensitive prostate cancer (CSPC).
Douglas McNeel (University of Wisconsin, Madison, USA) and study co-authors explain that the DNA vaccine pTVG-HP induces PAP-specific cytolytic CD8+ T cells, and as PAP is the target antigen of sipuleucel-T, an FDA-approved antitumor vaccine, this “validates PAP as a relevant prostate tumor antigen.”
In total, 97 men with a baseline prostate-specific antigen (PSA) level of at least 2 ng/mL, and a PSA doubling time of less than 12 months were randomly assigned to receive granulocyte-macrophage colony-stimulating factor (GM-CSF) at a dose of 200 µg with or without intradermal pTVG-HP 100 µg (MVI-816, Madison Vaccines, Wisconsin, USA) six times at 14-day intervals, and then quarterly for up to 2 years.
As reported in the Journal of Clinical Oncology, the primary endpoint of MFS rate at 2 years was achieved by 41.8% of the 48 men who received the vaccine and by a comparable 42.3% of the 49 who received GM-CSF alone.
Similarly, no significant difference was observed between men who were given the vaccine or not, in either median MFS (18.9 vs 18.3 months) – or on-treatment PSA doubling time (5.4 vs 8.9 months).
Stratified analysis showed that patients with the most rapidly progressive disease, whose PSA doubling times at baseline were below 3 months, had a significantly longer median MFS of 12.0 months if they received the vaccine, compared with 6.1 months if they only received GM-CSF. But there was no such difference among men with a longer doubling time.
McNeel et al say “[t]his was unexpected because we anticipated that a greater difference might be observed in patients with slower-growing disease,” and they postulate that despite “traditional schedules used for preventive vaccines, in which a limited number of treatments are used to establish long-term memory,” in this instance “the frequency of immunizations might need to be increased in the time period beyond 3 months.”
They continue: “Future trials will evaluate different booster treatment schedules.”
The researchers believe that combination treatments might improve the immunogenicity of cancer vaccines, and highlight previous research which suggests that combining DNA vaccines with PD-1 blockade results in PSA declines and tumor changes.
“A clinical trial that is evaluating pTVG-HP with PD-1 blockade in patients with castration-sensitive, PSA-recurrent prostate cancer is currently under way,” they conclude.
By Hannah Kitt
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