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PEER-TO-PEER CLINICAL CONVERSATIONS |
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Predicting Response to Bipolar Androgen Therapy: A Blood-Based Biomarker Approach
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Samuel Denmeade, MD
Alicia Morgans interviews Samuel Denmeade about the TRANSFORMER trial and Bipolar Androgen Therapy (BAT) for prostate cancer. Dr. Denmeade explains that the trial, involving 200 patients, compared high-dose testosterone therapy to enzalutamide in treating hormone-resistant prostate cancer.
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COMBAT Trial Yields Promising Results for Bipolar Androgen Therapy Plus Nivolumab in Metastatic Castration-Resistant Prostate Cancer
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Mark Markowski, MD, PhD, and Emmanuel Antonarakis, MD
Alicia Morgans, Mark Markowski, and Emmanuel Antonarakis discuss research on high-dose testosterone therapy for metastatic castration-resistant prostate cancer, inspired by Sam Denmeade's paradoxical approach.
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| Blood-Based Markers of Differential Efficacy of Bipolar Androgen Therapy and Enzalutamide in the Randomized TRANSFORMER Trial |
| Samuel R. Denmeade, MD |
| Samuel Denmeade presents findings from the TRANSFORMER trial, which compared Bipolar Androgen Therapy (BAT) to enzalutamide in CRPC. Results showed that BAT followed by enzalutamide led to longer progression-free survival and higher response rates than the reverse sequence. Blood-based markers, particularly androgen receptor (AR) alterations in circulating tumor DNA, were identified as potential predictors of treatment efficacy, with BAT being less effective for patients without AR alterations. |
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| Testosterone Is Not the Enemy…Reconsidering Treatment Options for Metastatic Castration-Resistant Prostate Cancer |
| Evan Yu, MD |
| This article explores the evolving role of supraphysiologic testosterone therapy, particularly Bipolar Androgen Therapy (BAT), in treating mCRPC. BAT leverages rapid testosterone cycling to induce DNA damage and apoptosis in prostate cancer cells, with promising results demonstrated in the TRANSFORMER trial, where BAT followed by enzalutamide improved progression-free survival (28.2 vs. 19.6 months) and overall survival (37.2 vs. 29.0 months) compared to the reverse sequence. |
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| Bipolar Androgen Therapy: Rationale, Candidate Patients, and Latest Evidence for mCRPC Patients |
| Rashid Sayyid, MD, MSc |
| Bipolar androgen therapy (BAT) exploits androgen receptor vulnerabilities in mCRPC by cycling between supraphysiologic and near-castrate testosterone levels. While BAT has shown potential to sensitize tumors to AR inhibitors, improve quality of life, and achieve durable responses in some patients, current evidence does not demonstrate a survival advantage over standard treatments. Ongoing trials are exploring BAT in combination with therapies like PARP inhibitors and immunotherapy to define its role in mCRPC care. |
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Response to Bipolar Androgen Therapy and PD-1 Inhibition in a Patient with Metastatic Castration-Resistant Prostate Cancer and a Germline CHEK2 Mutation - Beyond the Abstract
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| Benjamin Berger, MD, Matthew Labriola, MD, Emmanuel Antonarakis, MD, and Andrew Armstrong, MD, MSc |
| This case report highlights a patient with metastatic castration-resistant prostate cancer (mCRPC) and a germline CHEK2 mutation who showed a significant response to bipolar androgen therapy (BAT) followed by pembrolizumab. BAT led to a dramatic PSA decline and tumor burden reduction, improving his quality of life and extending survival to 21 months, far beyond the anticipated 6 months. While the role of pembrolizumab remains uncertain, the case underscores the potential of BAT in mCRPC, particularly for patients with DNA repair deficiencies, warranting further investigation. |
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