Re-posting a link to a prior post of mine that references a recently completed Phase 4 study of enzalutamide-treated patients with mCRPC who had progressive disease following prior abiraterone treatment from multiple clinical sites in Europe. It appears that median time to radiographic disease progression is ~8 months and median time to PSA progression is ~5.7 months. The basis for this Phase 4 trial was:

"....the European Medicines Agency requested the developers of enzalutamide to conduct a study to assess the efficacy of enzalutamide in patients who had progressed following abiraterone. In response, this postregistration study (ClinicalTrials.gov, NCT02116582) was performed to evaluate the efficacy and safety of enzalutamide treatment in patients with mCRPC following disease progression after at least 24 wk of abiraterone."

Antitumour Activity and Safety of Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Previously Treated with Abiraterone Acetate Plus Prednisone for ≥24 weeks in Europe

The above paper also cites a separate pooled analysis of previous studies of the efficacy of enzalutamide after docetaxel and abiraterone acetate treatment in mCRPC found "The median PFS was 3.1 months (range, 1.4-4.9 months)."

https://www.clinical-genitourinary-cancer.com/article/S1558-7673(14)00236-5/fulltext

These above referenced studies have relevance to the week 18 standard of care (SoC) line shown in the Zenith slides. I'm assuming this week 18 line is representing time to radiographic disease progression in patients who have progressed on prior abiraterone treatment and are now taking enzalutamide. I guess the take home here is that there is a lot of wiggle room in where one may draw a SoC line for enzalutamide alone. I don't think Zenith and/or the trial investigators are taking into account the finding of the recent Phase 4 trial in their representation of the week 18 SoC.

It would be extremely helpful if one of the stellar clinical trial investigators for this Zenith trial could present instead of Don in order to properly narrate and put into context. Sounds like a paper and conference presentation are in the works, so surely (hopefully?) better clarity will come from those.

In other mCRPC news, Astrazeneca and Merck announced yesterday at ASCO (and published yesterday in The Lancet Oncology) the results of a Phase 2 mCRPC trial. They found that in patients who have progressed on prior docetaxel first-line chemotherapy for mCRPC, that adding the PARP inhibitor LYNPARZA® (olaparib) to abiraterone  second-line therapy increased radiographic progression free survival from 8.2 months to 13.8 months. A great finding! To put this in the context of ZEN-3694 (and other BET inhibitors), enzalutamide + ZEN-3694 could be initiated after disease progression while on abiraterone alone (current Zenith combo trial) or abiraterone + olaparib (future trial?). Also of note, Zenith has already in their plans combo trials of ZEN-3694 with PARP inhibs. Not sure if they were planning on doing this in mCRPC or a different cancer, but these Merck/Astrazeneca ASCO results might influence their decision!

BearDownAZ