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A randomised comparison of high-dose testosterone against a standard hormone-blocking drug. Neither delayed progression better than the other, but men who had the testosterone first and the drug second lived nearly nine months longer before their second progression, and felt better throughout.
Samuel Denmeade and colleagues randomised 195 asymptomatic men with castration-resistant metastatic prostate cancer to monthly bipolar androgen therapy (94) or enzalutamide (101), with crossover permitted at progression. The primary endpoint was clinical or radiographic progression-free survival; the secondary endpoints included progression-free survival from randomisation through crossover, which the authors call PFS2.
On the primary endpoint the trial is flat: 5.7 months in both arms. The interesting result is the sequence effect. Prostate-specific antigen progression-free survival on enzalutamide was 3.8 months when it followed abiraterone and 10.9 months when it followed bipolar androgen therapy, and PFS2 was 28.2 months for the bipolar-then-enzalutamide sequence against 19.6 months for the reverse. Quality of life consistently favoured bipolar androgen therapy. The trial is the reason the approach is worth a phase 3, and PFS2 is the endpoint that phase 3 would need.
The first randomised evidence that the order in which prostate cancer treatments are given changes how long they work, independently of which treatments they are. It is also a rare trial in which quality of life pointed one way and the primary endpoint pointed nowhere.
A demonstration that a drug that has stopped working can be made to work again by changing the environment the tumour has adapted to, rather than by changing the drug. It is the strongest clinical evidence in prostate cancer for treating resistance as something reversible.
One technology page, one pathway page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
The reason intermittent androgen deprivation is offered as a choice in metastatic disease rather than recommended, and a case study in what an inconclusive non-inferiority trial should say. For a man weighing the side effects, the honest statement is that the quality-of-life gain is real but brief and the survival question is open.
Shares Radiographic progression-free survival (rPFS), Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint, Randomise the order of treatment, not only the drugs: a strategy platform for metastatic prostate cancer, PSA (prostate-specific antigen) and the tag prostate-evidence.
Shares RESTORE: bipolar androgen therapy after progression on enzalutamide in metastatic castration-resistant prostate cancer, Bipolar androgen therapy (BAT), Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint, Enzalutamide and the tag prostate-evidence.
Shares Radiographic progression-free survival (rPFS), Quality of life, PSA (prostate-specific antigen), Enzalutamide and the tag prostate-evidence.
Shares Radiographic progression-free survival (rPFS), PSA (prostate-specific antigen), Enzalutamide, Castration-resistant prostate cancer (CRPC) and the tag prostate-evidence.
Shares Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint, Castration-resistant prostate cancer (CRPC), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Androgen receptor and the tag prostate-evidence.
Shares PSA (prostate-specific antigen), Abiraterone acetate, Castration-resistant prostate cancer (CRPC), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch and the tag prostate-evidence.
Shares Quality of life, PSA (prostate-specific antigen), Castration-resistant prostate cancer (CRPC), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch and the tag prostate-evidence.
Shares PSA (prostate-specific antigen), Castration-resistant prostate cancer (CRPC), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Acquired resistance to every therapy and the tag prostate-evidence.