Background: Chemotherapy remains the mainstay of treatment for early-stage triple negative breast cancer (TNBC), yet targetable drivers of interest are under investigation. A subset of TNBCs express the androgen receptor (AR) and exhibit androgen-dependent growth. The AR-antagonist enzalutamide (ENZA) has shown activity in patients with metastatic AR+ TNBC. In this study, the feasibility of adjuvant ENZA in early-stage, AR+ TNBC was assessed (NCT02750358). As reported previously, this study met its primary endpoint of feasibility (Traina et al., ASCO 2019). Here we report secondary survival endpoints. Methods: In this single-arm, open-label, multi-center trial, patients with stage I-III, AR≥1% TNBC (ER/PR <1%, HER2 negative) who had completed standard of care therapy were treated with ENZA 160 mg/day orally for 1 year. Patients who completed 1 year had an option to remain on adjuvant ENZA for another year. Toxicity was graded using National Cancer Institute Common Toxicity Criteria (NCI CTCAE) v4. The primary endpoint of this study was to evaluate feasibility of adjuvant ENZA, defined as the discontinuation rate due to toxicity, withdrawal of consent, other events related to tolerability or patient preference. The study was designed to discriminate between feasibility rates of 50% and 70% and was considered feasible if ≥29 out of 46 patients received ENZA for one year without discontinuation. Secondary endpoints included DFS, OS, safety, patient reported outcomes and correlative science. Patients who had disease progression (PD) during year 1 of ENZA without treatment discontinuation due to the above reasons were not included in the primary feasibility analysis but were included in secondary endpoint analyses for survival. Results: 50 patients enrolled on study from 05/2016 - 06/2018. The median age was 58 years (range 34-81 years); 8% had a germline BRCA1/2 (n=3) or PALB2 (n=1) mutation. 38% had stage I disease at diagnosis, 48% stage II and 14% stage III. 74% had grade 3 tumors. 94% of all patients received prior systemic chemotherapy, 81% of whom received prior anthracycline-taxane. 38% (n=19) were treated with prior neoadjuvant chemotherapy and 32% of those patients (n=6) achieved a pCR. Of those who did not achieve a pCR, 69% received adjuvant capecitabine. 47 patients were evaluable for the study endpoint and 35 patients completed 1 year of ENZA thereby meeting the prespecified trial endpoint for feasibility. 32 patients elected to continue into a second year of treatment. After a median follow-up of 140 weeks (range 4 - 236 weeks), 8 patients had a DFS event: 7 TNBC recurrences and 1 new primary breast cancer. The 1-year DFS was 94% (95% CI: 87 - 100%), 2-year DFS was 92% (95% CI: 84 - 99.8%) and the 3-year DFS was 80% (95% CI: 67 - 94%). The median DFS and OS have not yet been reached. Two patients died of TNBC recurrence after 55 and 59 weeks. There were no new or unexpected toxicities observed at study completion. Conclusion: This single-arm trial previously met its primary endpoint of feasibility in patients with early-stage AR+ TNBC. In this relatively high-risk, albeit highly selected patient population, the 3-year DFS measured 80% (95% CI: 67 - 94%) with an adjuvant endocrine therapy approach. Efforts to determine the optimal biomarker for AR+ TNBC are ongoing, so that patients most likely to respond to AR-antagonists in both the early and metastatic setting may be identified. Biomarker data from this study including PD-L1 status and tumor sequencing will be reported at the time of presentation.Funding and drug support for this study was provided by Astellas Pharma Global Development Inc./Pfizer Inc.
Citation Format: Elaine M Walsh, Ayca Gucalp, Sujata Patil, Marcia Edelweiss, Dara S Ross, Pedram Razavi, Shanu Modi, Neil M Iyengar, Rachel Sanford, Tiffany Troso-Sandoval, Mila Gorsky, Jackie Bromberg, Pamela Drullinsky, Diana Lake, Serena Wong, Patricia DeFusco, Nicholas Lamparella, Ranja Gupta, Tasmila Tabassum, Leigh Ann Boyle, Artavazd Arumov, Tiffany A Traina. Adjuvant enzalutamide for the treatment of early-stage androgen-receptor positive, triple negative breast cancer: A feasibility study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-14-03.