RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:BioWorld-Interesting article G1945V,
Provenge is not a cure for mCRPC. It has no effect on time to disease progression and doesn't stop the cancer from growing. It somehow benefits the patient to squeeze out on average 4.1 months of life as stated in the NEJM article I linked to earlier. So although this "vaccine" is boosting the immune system to attack prostate cancer cells, it apparently isn't causing the prostate cells to under cell death/apoptosis and not shrinking the tumor. The NEJM authors speculate that this "may be due to the delayed onset of antitumor responses after active immunotherapy, relative to objective disease progression, which occurred early in this group of patients."
ZEN-3694 on the other hand, via direct inhibition of BET proteins in the prostate cancer tumor cells, has been shown to have profound effects on stopping the proliferation of prostate cancer cells via transcriptional effects on tumor growth gene expression. This has been shown in various prostate cancer cell lines treated with or without ZEN-3694 in vitro as well as in mouse xenograft models in which they place these prostate cancer cell lines into the mouse and treat the mouse with ZEN-3694. So ZEN-3694, unlike provenge, would seem to be able to halt the proliferation of the prostate cancer cells and prevent the prostate cancer from growing. Part of this is because ZEN-3694 works downstream of current androgen deprivation therapies to directly inhibit the ability of BET proteins to promote tumor growth gene expression. ZEN-3694 also promotes some anti-tumor immune responses and modulates various immuno-oncology targets. These immuno-oncology and anti-tumor immune responses might overlap with some of the mechanism of action of Provenge, but I don't know for sure.
Long story short......both ZEN-3694 and Provenge are going after the same patient population. However, Provenge has already been shown in Phase 3 trials to be unable to cure prostate cancer, unable to stop prostate cancer progression, and add only 4.1 months of life on average. ZEN-3694 is only in Phase 1 and the hope is that due to its pre-clinical effects on halting prostate cancer cell proliferation and tumor growth, that ZEN-3694 will offer a much more robust life-lengthening, tumor stabilizing/shrinking response than Provenge and either offer these effects as a stand alone therapy or in combination with other androgen deprivation therapies, chemotherapeutics, or immuno-oncology agents.
From the cancer.org page I linked to earlier:
"Sipuleucel-T (Provenge) is a cancer vaccine. Unlike traditional vaccines, which boost the body’s immune system to help prevent infections, this vaccine boosts the immune system to help it attack prostate cancer cells. The vaccine is used to treat advanced prostate cancer that is no longer responding to initial hormone therapy but that is causing few or no symptoms. The vaccine hasn’t been shown to stop prostate cancer from growing, but it seems to help men live an average of several months longer. As with hormone therapy and chemotherapy, this type of treatment has not been shown to cure prostate cancer."
From the NEJM article I linked to earlier: "The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed."
Also from the NEJM article: "In contrast to overall survival, the time to objective disease progression as defined in this study did not differ significantly between the study groups. This result is consistent with the findings in previous trials of sipuleucel-T and may be due to the delayed onset of antitumor responses after active immunotherapy, relative to objective disease progression, which occurred early in this group of patients.32 In patients with metastatic castration-resistant prostate cancer, the disease-progression end point, as currently defined, has not been a reliable predictor of overall survival. Several randomized trials that have shown effects of various treatments on overall survival have not shown effects on disease progression14,28,29 and vice versa,7 including one study in which a therapeutic prostate cancer vaccine was administered in a patient population similar to ours,29 suggesting a possible class effect or some previously unknown feature of prostate cancer."