The AR inhibitor enzalutamide achieved responses in patients with advanced TNBC in a phase II trial.

  • Major finding: The AR inhibitor enzalutamide achieved responses in patients with advanced TNBC in a phase II trial.

  • Clinical relevance: Enzalutamide is well tolerated and achieves a 33% clinical benefit rate in patients with TNBC.

  • Impact: The subset of patients with AR-positive TNBC may benefit from AR inhibition with enzalutamide.

Patients with triple-negative breast cancer (TNBC), which lacks expression of the estrogen and progesterone receptors, have a poorer prognosis than patients with other breast cancer subtypes. Therapeutic targets have yet to be identified for most patients with TNBC, but a subset of tumors are androgen-receptor (AR) positive and may be driven by AR signaling, suggesting that AR inhibition may be beneficial in these patients. Further, AR inhibitors have demonstrated antitumor activity in preclinical and early clinical studies. Traina and colleagues evaluated the safety and antitumor activity of the AR inhibitor enzalutamide in a single-arm, open-label, phase II trial of 118 patients with locally advanced or metastatic AR-positive TNBC. The primary endpoint was the clinical benefit rate (CBR) at 16 weeks. Secondary endpoints included the CBR at 24 weeks, progression-free survival, and safety. The CBR at 16 weeks was 33% in the 78 evaluable patients, including one complete response and 5 partial responses, median progression-free survival was 3.3 months, and median overall survival was 17.6 months. Enzalutamide was well tolerated, and no treatment-related serious adverse events were reported. The safety profile was consistent with what had previously been reported; the most frequent grade 3+ adverse event was fatigue, which occurred in 3.4% of patients. Taken together, the results of this phase II trial indicate that AR inhibition with enzalutamide is well tolerated and has antitumor activity in patients with AR-positive TNBC, supporting its further clinical investigation in these patients.

Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O'Shaughnessy J, et al. Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. J Clin Oncol 2018 Jan 26 [Epub ahead of print].

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