Enzalutamide Phase 2 study for AR positive triple-negative breast cancer meets primary endpoint

Astellas Pharma Inc. (Tokyo: 4503) announced that data from a Phase 2 study evaluating the investigational use of enzalutamide as a single agent for the treatment of advanced androgen receptor (AR) positive, triple-negative breast cancer (TNBC) were presented during an oral abstracts session at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The study met its primary endpoint and the abstract was also selected to be featured in the upcoming 'Best of ASCO' meetings.

The Phase 2 open label single arm, multicenter trial enrolled 118 women with advanced TNBC in two stages. The primary endpoint of the trial was clinical benefit rate at 16 weeks (CBR16), defined as the proportion of women with a complete response (CR), partial response (PR) or stable disease for at least 16 weeks. Two patient populations were evaluated in this study: the Evaluable patient population had at least 10 percent of the cells in their primary tumor sample test positive for the AR and had at least one follow up tumor assessment, while the Intent-To-Treat population (ITT) received at least one dose of enzalutamide and their breast cancer had any amount of AR immunohistochemistry staining present. 75 patients met the criteria for the Evaluable population and a total of 118 patients were included in the ITT population. There was no limit to the number of prior treatments received.

• In the 75 Evaluable patients, CBR16 was achieved in 35% (95% CI: 24-46) including six CR/PR (8%). Clinical benefit rate at ≥ 24 weeks (CBR24) was achieved in 29% (95% CI: 20-41). The median progression-free survival (PFS) was 14.7 weeks (95% CI: 8.1-19.3).
• In the ITT population, CBR16 was achieved in 25% (95% CI: 17-33) including seven CR/PR (6%). CBR24 was achieved in 20% (95% CI: 14-29). Median PFS was 12.6 weeks (95% CI: 8.1-15.7).

Data collected in this study enabled the development of a novel genomic assay. The diagnostic assay, which was also introduced during a poster abstract session at ASCO, was assessed for its ability to identify patients who may benefit from enzalutamide. Approximately 50 percent of the ITT population were diagnostic positive and data according to this methodology were as follows:

• In the ITT, 39% (95% CI: 27-53) of patients with diagnostic positive AR TNBC achieved CBR16 and 36% achieved CBR24 (95% CI: 24-49), whereas 11% (95% CI: 5-21) of patients with diagnostic negative AR TNBC achieved CBR16 and only 6% (95% CI: 2-16) achieved CBR24. mPFS was 16.1 weeks (95% CI: 13.3, 27.4) compared with 8.1 weeks (95% CI: 7.4, 12.6), respectively.
• Diagnostic positive AR TNBC patients treated with enzalutamide as their first or second line of treatment in the ITT population demonstrated a median PFS of 40.4 weeks (95% CI: 16.1- not yet reached) compared with 8.9 weeks (95% CI: 7.3, 15.7) in patients with diagnostic negative AR TNBC disease.

The most common (reported in ≥10%) related adverse events in the ITT were fatigue (34%), nausea (25%), decreased appetite (13%), diarrhea and hot flush (10% each).

Best of ASCO
The 'Best of ASCO' Meetings condense the most cutting-edge science and education from the world's premier oncology event, the ASCO Annual Meeting, into a two-day program. The abstracts chosen for presentation and discussion reflect the foremost research and strategies in oncology that have the greatest potential to directly impact patient care.