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Bicalutamide Plus Aromatase Inhibitor in Patients with Estrogen Receptor-Positive/Androgen Receptor-Positive Advanced Breast Cancer.

Abstract

LESSONS LEARNED

Studies targeting the androgen receptor (AR) signaling pathway in aromatase inhibitor (AI)-resistant breast cancer are limited.Bicalutamide, one of the commonly used AR inhibitors in prostate cancer, in combination with AI, did not show synergistic activity in patients with estrogen receptor-positive and AI-resistant disease in this phase II, single-arm study.The clinical benefit rate and objective response rate at 6 months were 16.7% and 0%, respectively, and the study was terminated after the first stage.

BACKGROUND

Endocrine resistance is a major problem in clinical practice. Studies have shown that androgen receptor (AR) signaling activation may be one of the mechanisms, and targeting AR showed some promising results in AR-positive triple-negative breast cancer. The aim of this study was to assess the efficacy and safety of bicalutamide plus another aromatase inhibitor in patients with nonsteroidal aromatase inhibitor (AI) or steroidal AI resistance and estrogen receptor (ER)-positive and AR-positive advanced breast cancer.

METHODS

A Simon's two-stage, phase II, single-arm study was conducted. We assumed the clinical benefit rate (CBR) of 40% would be significant in clinical practice. In this case, if ≥4 patients of the 19 patients in the first stage benefited from treatment, the CBR would achieve the assumed endpoint. If fewer than four patients benefited from treatment in the first stage, the trial would be terminated. All patients received bicalutamide 50 mg per day orally plus another aromatase inhibitor. The primary outcome was CBR; secondary outcomes included objective response rate (ORR), progression-free survival (PFS), and tolerability.

RESULTS

A total of 19 patients enrolled in the first stage, and 18 patients met all criteria for analysis. The trial terminated according to protocol after the first stage. After a median follow-up of 14 months, the CBR at 6 months was 16.7% (3/18); no patients with partial or complete response were observed. The median PFS was 2.7 months. Bicalutamide in combination with AI was well tolerated.

CONCLUSION

Bicalutamide in combination with another AI did not show synergistic activity in patients with ER-positive breast cancer and AI resistance. Results suggest that no more large-sample clinical trials should be conducted in this population for overcoming endocrine resistance.

Authors+Show Affiliations

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China xufei@sysucc.org.cn wangshs@sysucc.org.cn.Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China xufei@sysucc.org.cn wangshs@sysucc.org.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31434793

Citation

Lu, Qianyi, et al. "Bicalutamide Plus Aromatase Inhibitor in Patients With Estrogen Receptor-Positive/Androgen Receptor-Positive Advanced Breast Cancer." The Oncologist, 2019.
Lu Q, Xia W, Lee K, et al. Bicalutamide Plus Aromatase Inhibitor in Patients with Estrogen Receptor-Positive/Androgen Receptor-Positive Advanced Breast Cancer. Oncologist. 2019.
Lu, Q., Xia, W., Lee, K., Zhang, J., Yuan, H., Yuan, Z., ... Xu, F. (2019). Bicalutamide Plus Aromatase Inhibitor in Patients with Estrogen Receptor-Positive/Androgen Receptor-Positive Advanced Breast Cancer. The Oncologist, doi:10.1634/theoncologist.2019-0564.
Lu Q, et al. Bicalutamide Plus Aromatase Inhibitor in Patients With Estrogen Receptor-Positive/Androgen Receptor-Positive Advanced Breast Cancer. Oncologist. 2019 Aug 21; PubMed PMID: 31434793.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bicalutamide Plus Aromatase Inhibitor in Patients with Estrogen Receptor-Positive/Androgen Receptor-Positive Advanced Breast Cancer. AU - Lu,Qianyi, AU - Xia,Wen, AU - Lee,Kaping, AU - Zhang,Jingmin, AU - Yuan,Huimin, AU - Yuan,Zhongyu, AU - Shi,Yanxia, AU - Wang,Shusen, AU - Xu,Fei, Y1 - 2019/08/21/ PY - 2019/04/23/received PY - 2019/07/22/accepted PY - 2019/8/23/pubmed PY - 2019/8/23/medline PY - 2019/8/23/entrez JF - The oncologist JO - Oncologist N2 - LESSONS LEARNED: Studies targeting the androgen receptor (AR) signaling pathway in aromatase inhibitor (AI)-resistant breast cancer are limited.Bicalutamide, one of the commonly used AR inhibitors in prostate cancer, in combination with AI, did not show synergistic activity in patients with estrogen receptor-positive and AI-resistant disease in this phase II, single-arm study.The clinical benefit rate and objective response rate at 6 months were 16.7% and 0%, respectively, and the study was terminated after the first stage. BACKGROUND: Endocrine resistance is a major problem in clinical practice. Studies have shown that androgen receptor (AR) signaling activation may be one of the mechanisms, and targeting AR showed some promising results in AR-positive triple-negative breast cancer. The aim of this study was to assess the efficacy and safety of bicalutamide plus another aromatase inhibitor in patients with nonsteroidal aromatase inhibitor (AI) or steroidal AI resistance and estrogen receptor (ER)-positive and AR-positive advanced breast cancer. METHODS: A Simon's two-stage, phase II, single-arm study was conducted. We assumed the clinical benefit rate (CBR) of 40% would be significant in clinical practice. In this case, if ≥4 patients of the 19 patients in the first stage benefited from treatment, the CBR would achieve the assumed endpoint. If fewer than four patients benefited from treatment in the first stage, the trial would be terminated. All patients received bicalutamide 50 mg per day orally plus another aromatase inhibitor. The primary outcome was CBR; secondary outcomes included objective response rate (ORR), progression-free survival (PFS), and tolerability. RESULTS: A total of 19 patients enrolled in the first stage, and 18 patients met all criteria for analysis. The trial terminated according to protocol after the first stage. After a median follow-up of 14 months, the CBR at 6 months was 16.7% (3/18); no patients with partial or complete response were observed. The median PFS was 2.7 months. Bicalutamide in combination with AI was well tolerated. CONCLUSION: Bicalutamide in combination with another AI did not show synergistic activity in patients with ER-positive breast cancer and AI resistance. Results suggest that no more large-sample clinical trials should be conducted in this population for overcoming endocrine resistance. SN - 1549-490X UR - https://www.unboundmedicine.com/medline/citation/31434793/Bicalutamide_Plus_Aromatase_Inhibitor_in_Patients_with_Estrogen_Receptor-Positive/Androgen_Receptor-Positive_Advanced_Breast_Cancer L2 - http://theoncologist.alphamedpress.org/cgi/pmidlookup?view=long&pmid=31434793 DB - PRIME DP - Unbound Medicine ER -