Eleni Efstathiou, MD, PhD of the University of Texas MD Anderson Cancer Center, Houston, Texas, TX, provides an overview of the Phase II trial of leuprolide acetate (LHRHa) and abiraterone acetate with or without ENZA (neoadjuvant enzalutamide) in high-risk prostate cancer (NCT01946165). Dr Efstathiou explains that the trial should not be considered as an independent trial, but as one in a series of companion trials. She explains that novel agents that are available from the more advanced disease settings, to explore what may be happening at a tumor micro-environment level, and treating patients and sampling their cancers. This was done in the metastatic castrate-resistant prostate cancer, looking at the bone micro-environment in the past years. She further discusses the presentation regarding the first trial of the neoadjuvant comparing the combination of the approved drugs abiraterone acetate and enzalutamide vs. abiraterone acetate combined with LHRHa in men with a high risk, localized disease. Dr Efstathiou explains that with all the new guidelines coming forth, even if these male patients get a prostatectomy, or even if they follow the approach of a combination of both radiation and LHRH for 2-3 years, there will be a very significant subset of these men who will relapse. She further explains that this trial addressed the unmet need set out above. She reflects on the talks last year, where the use of abiraterone plus LHRHa was suggested to be a good idea for new adjuvant treatment for these men given that it induces hydroreduction. Now, researchers are looking for an even better readout with a combination. She proceeds to explain that the abiraterone with LHRHs combination worked better than the 3-drug combination. At that point, the question asked was ‘Was there a drug-drug interaction?’. However, there was no indication of this. Following this, she explains that markers were then studied. In the 3-drug combination, more of the potential markers for primary resistance were found. Finally, all the cancers that seemed to be resisting the treatment were then studied; this analysis showed that there was an association with phosphatase and tensin homolog (PTEN) loss that had also been reported pre-clinically. This trial therefore proved to be very informative in finding out what is happening at the tumor micro-environment level. Recorded at the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO), held in Chicago, IL.