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SHR Neuro Krebs Kardio Lipid

Lu, C; Terbuch, A; Dolling, D; Yu, J; Wang, H; Chen, Y; Fountain, J; Bertan, C; Sharp, A; Carreira, S; Isaacs, WB; Antonarakis, ES; De Bono, JS; Luo, J.
Treatment with abiraterone and enzalutamide does not overcome poor outcome from metastatic castration-resistant prostate cancer in men with the germline homozygous HSD3B1 c.1245C genotype.
Ann Oncol. 2020;
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Autor/innen der Med Uni Graz:
Terbuch Angelika
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Abstract:
In men with castration-sensitive prostate cancer (CSPC), the HSD3B1 c.1245A>C variant has been reported to associate with shorter responses to first-line androgen deprivation therapy (ADT). Here, we evaluated the association between the inherited HSD3B1 c.1245A>C variant and outcomes from metastatic castration-resistant prostate cancer (mCRPC) after first-line abiraterone (Abi) or enzalutamide (Enza). Patients (n=266) with mCRPC were enrolled from two centers at the time of starting first-line Abi/Enza. Outcomes after Abi/Enza included best PSA response, treatment duration, and overall survival (OS). Outcomes after first-line ADT were determined retrospectively, and included treatment duration and OS. As was pre-specified, we compared patients with the homozygous variant HSD3B1 genotype (CC genotype) versus the combined group with the heterozygous (AC) and homozygous wild-type (AA) genotypes. Among the 266 patients, 22 (8.3%) were homozygous for the HSD3B1 variant (CC). The CC genotype had no association with PSA response rate; the median Abi/Enza treatment duration was 7.1 months for the CC group and 10.3 months for the AA/AC group (log rank p=0.34). Patients with the CC genotype had significantly worse OS, with median survival at 23.6 months for the CC group and 30.7 months for the AA/AC group (log rank p=0.02). In multivariable analysis adjusting for age, Gleason, PSA, prior chemotherapy, and M1 disease, the association between the CC genotype and OS remained significant (HR: 1.78, 95% CI: 1.03-3.07, p=0.04). Poor outcome after first-line ADT in the CC group was also observed when evaluating retrospective ADT duration data for the same combined cohort. In this large two-center study evaluating the HSD3B1 c.1245 genotype and outcomes after first-line Abi/Enza, homozygous variant (CC) HSD3B1 genotype was associated with worse outcomes. Novel therapeutic strategies are needed to enable treatment selection based on this genetic marker. Copyright © 2020. Published by Elsevier Ltd.

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