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Enzalutamide, an oral tablet that blocks the androgen receptor at several points at once, added nearly five months to median survival in men whose cancer had already been through chemotherapy. More than half had their PSA halve, against two percent on placebo.
Howard Scher and the AFFIRM investigators randomised 1,199 men with castration-resistant prostate cancer who had already had chemotherapy, in a 2 to 1 ratio, to 160 mg of enzalutamide daily or placebo. The trial was stopped at a planned interim analysis after 520 deaths.
Enzalutamide came out of the Sawyers laboratory as a direct answer to the biology described in Chen 2004: a compound that stays an antagonist when the androgen receptor is abundant, and that also blocks nuclear translocation and DNA binding. AFFIRM is the clinical proof that the design brief was right. Every secondary endpoint moved in the same direction, which is unusual, and the effect size on prostate-specific antigen (54 percent against 2 percent) is among the largest in solid tumour oncology.
An oral drug that works after chemotherapy has failed, in a disease where the previous option was more chemotherapy. Together with abiraterone it moved castration-resistant prostate cancer from a chemotherapy disease to a hormonal one, and set up the sequencing questions the field is still arguing about.
The trial that made an androgen receptor inhibitor the usual first treatment for castration-resistant prostate cancer, and that delayed chemotherapy by a long margin for most men. Its effect sizes are why later trials in this setting are judged against a hazard ratio near 0.7 for survival.
Abiraterone became a standard treatment for metastatic castration-resistant prostate cancer and, after later trials, for hormone-sensitive and high-risk localised disease.
Proof that a cancer resistant to one taxane is not resistant to all of them, and the beginning of treatment sequencing in castration-resistant disease. The CARD trial later showed that after an androgen receptor drug has failed, cabazitaxel beats switching to the other androgen receptor drug.
Shares Molecular determinants of resistance to antiandrogen therapy, Radiographic progression-free survival (rPFS), PSA (prostate-specific antigen), 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 COU-AA-301: abiraterone and increased survival in metastatic castration-resistant prostate cancer after docetaxel, Molecular determinants of resistance to antiandrogen therapy, PSA (prostate-specific antigen), Castration-resistant prostate cancer (CRPC) and the tag prostate-evidence.
Shares TROPIC: prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel, Quality of life, PSA (prostate-specific antigen), Castration-resistant prostate cancer (CRPC) and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, PSA (prostate-specific antigen), Enzalutamide, Castration-resistant prostate cancer (CRPC) and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, Quality of life, PSA (prostate-specific antigen), Enzalutamide and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, 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), 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.