HSD3B1 genotype and outcomes in metastatic hormone-sensitive prostate cancer with androgen deprivation therapy and enzalutamide: ARCHES.
Cell Rep Med
; 5(8): 101644, 2024 Aug 20.
Article
in En
| MEDLINE
| ID: mdl-39168093
ABSTRACT
HSD3B1 encodes 3ß-hydroxysteroid dehydrogenase-1, which converts adrenal dehydroepiandrosterone to 5α-dihydrotestosterone and is inherited in adrenal-permissive (AP) or adrenal-restrictive forms. The AP allele is linked to castration resistance, mainly in low-volume tumors. Here, we investigate the association of HSD3B1 alleles with outcomes in ARCHES, a multinational, double-blind, randomized, placebo-controlled phase 3 trial that demonstrated clinical benefit with enzalutamide plus androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC) compared to those treated with placebo plus ADT. There are no significant differences between genotypes for clinical efficacy endpoints. Enzalutamide significantly improves radiographic progression-free survival and overall survival vs. placebo irrespective of HSD3B1 status. Men with the AP genotype have higher post-progression mortality and treatment-emergent adverse events, including hypertension, cardiovascular events, and gynecomastia, but a lower fracture rate. Overall, enzalutamide is beneficial in men with mHSPC independent of the HSD3B1 genotype. Inherited polymorphisms of HSD3B1 may account for differential toxicities.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenylthiohydantoin
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Progesterone Reductase
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Steroid Isomerases
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Benzamides
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Genotype
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Androgen Antagonists
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Multienzyme Complexes
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Nitriles
Limits:
Aged
/
Humans
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Male
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Middle aged
Language:
En
Journal:
Cell Rep Med
Year:
2024
Document type:
Article