Experience of bipolar androgen therapy (BAT) in Argentinian oncology centres

Martín Zarbá; Martin Angel; Federico Losco; Juan José Zarbá; Juan Carlos Pupilli; Matías Rodrigo Chacon; Juan Pablo Sade

doi:10.3332/ecancer.2022.1480

Experience of bipolar androgen therapy (BAT) in Argentinian oncology centres

Ecancermedicalscience. 2022 Dec 2:16:1480. doi: 10.3332/ecancer.2022.1480. eCollection 2022.

Authors

Martín Zarbá^{1

2}, Martin Angel^{3

4

5}, Federico Losco^{3

6}, Juan José Zarbá^{7

8}, Juan Carlos Pupilli⁹, Matías Rodrigo Chacon^{10

11}, Juan Pablo Sade^{3

12}

Affiliations

¹ FUCA, Instituto Alexander Fleming, CABA C1426ANZ, Argentina.
² https://orcid.org/0000-0003-3642-4035.
³ Genitourinary Tumors Department, Instituto Alexander Fleming, CABA C1426ANZ, Argentina.
⁴ These authors have contributed equally to this work.
⁵ https://orcid.org/0000-0002-1463-8887.
⁶ https://orcid.org/0000-0001-5084-3012.
⁷ Oncology Department, Hospital Zenon Santillan, San Miguel de Tucuman T4000IAK, Argentina.
⁸ https://orcid.org/0000-0003-1013-3993.
⁹ Genitourinary Tumors Department, Sanatorio Británico Rosario, Santa Fé S2000ANZ, Argentina.
¹⁰ Oncology Department, Instituto Alexander Fleming, CABA C1426ANZ, Argentina.
¹¹ https://orcid.org/0000-0001-6872-4185.
¹² https://orcid.org/0000-0001-9312-5280.

Abstract

Background: Previous studies with bipolar androgen therapy (BAT) have shown clinical activity in metastatic Castration Resistant Prostate Cancer (mCRPC) as well as the potential to re-sensitise prostate cancer cells to prior androgen receptor-targeted agents. None of these studies had tested BAT after chemotherapy. In this study, we gathered real-world evidence from three centres in Argentina where BAT is being used in castration-resistant prostate cancer (CRPC), not only prior to chemotherapy but also after several lines of treatment.

Materials and methods: This retro-prospective nonrandomised multicentre cohort study included patients with mCRPC, who received BAT in different scenarios defined by the treating physician at three centres in Argentina.

Results: A total of 21 asymptomatic patients with mCRPC were included. There was a median of two lines before BAT, with nine patients (42.8%) receiving three or more lines, and 13 patients (61.9%) receiving chemotherapy previously. Previous lines included next-generation hormonal agents (NHA) in 100% (abiraterone 33.3% and enzalutamide 71.4%), chemotherapy in 61.9%, Radium-223 in 47.6% and others in 4.8%. The progression free survival (PFS) after BAT was 3.5 months (95% CI: 3.06-7.97). PSA50 response rate (RR) was 28.5% and the overall RR was 14.3%. Of the 17 patients who had disease progression, 9 had a rechallenge to NHA, achieving a 55% RR, 6 received other treatment (chemotherapy in 5 and ¹⁷⁷Lu-PSMA in 1) with a 66% RR and 2 best supportive care. The PFS2, calculated after the initiation of BAT in the 15 patients who received further therapy, was 7.93 months (95% CI: 6.73-NR). Treatment was overall well tolerated, with only two patients requiring hospitalisation and treatment interruption due to worsening pain.

Conclusion: To the authors' knowledge, this is the first publication of BAT in later lines of therapy in mCRPC. BAT showed clinical activity in this scenario. Our data supports that BAT may play a role in CRPC re-sensitisation after multiple treatment lines.

Keywords: androgen deprivation; castration resistance; supraphysiological testosterone.