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Sandy Srinivas, MD
Sandy Srinivas, MD
Posted: Thursday, February 23, 2023
To discern the real-world effectiveness of darolutamide in a racially or ethnically diverse population of patients with metastatic castration-resistant prostate cancer, Nicholas Mitsiades, MD, of Baylor College of Medicine, Houston, and colleagues focused on the use of this second-generation androgen receptor (AR) antagonist in those with prior exposure to CYP17 inhibitors and/or other second-generation AR antagonists (such as enzalutamide or apalutamide). Although sequential treatment with darolutamide in this patient population may be of benefit for some patients, the investigators found that prior resistance to other AR antagonists and/or associated AR mutations may decrease the likelihood of benefit. These findings were presented at the 2023 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium (Abstract 150).
Clinical data from patients with advanced prostate cancer who received their care at Houston’s Ben Taub Hospital were abstracted by the study authors. They identified 33 patients with M1 castration-resistant prostate cancer (17 Black, 14 Hispanic White, 1 non-Hispanic White, 1 Asian) and 4 patients with M0 castration-resistant prostate cancer (2 non-Hispanic Black, 2 Hispanic White) who received darolutamide at this safety-net public hospital.
For the entire M1 cohort, progression-free survival rates at 3, 6, and 12 months were 36%, 10%, and 5%, respectively. For patients who experienced prior resistance to CYP17 inhibitors—but not to second-generation AR antagonists—progression-free survival rates at 3, 6, and 12 months were 42%, 17%, and 8%, respectively. For those who had prior resistance to second-generation AR antagonists, progression-free survival rates at 3, 6, and 12 months were 25%, 0%, and 0%, respectively. Finally, for those who had AR mutations detected before treatment with darolutamide, progression-free survival rates at 3, 6, and 12 months were 31%, 0%, and 0%, respectively.
“AR mutations that emerged or increased in ctDNA allele fraction while on darolutamide included L702H, H875Y, H100Q, D891H, T878A, L329W, and AR copy number gain, suggesting a possible role in darolutamide resistance,” the investigators noted.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
2023 ASCO GU Cancers Symposium
