Mutations of SPOP (mtSPOP) as Treatment Selection Biomarkers

Oct 5, 2022

For patients with mCSPC, the current standard of treatment is to intensify androgen deprivation therapy (ADT) with docetaxel or androgen receptor axis-targeted therapy (ARAT: abiraterone, apalutamide, enzalutamide). But there aren’t enough indicators to help with therapy decision-making. Researchers had previously demonstrated that ADT enhanced the survival results for dn-mCSPC patients with mtSPOP. In that case, they predicted that mtSPOP would be linked to better results with ARAT + ADT but not with docetaxel + ADT.

The study made use of the countrywide (US-based) de-identified Flatiron Health-Foundation Medicine Prostate Cancer clinico-genomic database (FH-FMI CGDB), which contained de-identified information from about 280 US cancer treatment facilities (∼800 sites of care). Included conditions include having dn-mCSPC, having a tissue biopsy 90 days after the diagnosis, and starting ARAT or docetaxel + ADT within 120 days. With Cox proportional hazards models modified for baseline prognostic variables, including PSA and ECOG, time to castration-resistance (TTCR) and overall survival (OS), indexed from metastatic diagnosis, were assessed. To account for eternal time, OS risk intervals in the complete genomic profile report have been left trimmed to date.

A total of 423 of the 4,089 points in the FH-FMI CGDB satisfied the inclusion requirements. ADT + ARAT was given to 215 people, while ADT + docetaxel was given to 208 people. About 37 pts, or 8.7%, were mtSPOP(+). In comparison to wild-type SPOP (wtSPOP), patients with mtSPOP who received ARAT had better median TTCR and OS. On the other hand, results on docetaxel were not related to SPOP status. Tests looking for treatment interaction had significant results.

In the real-world investigation, mtSPOP was linked to better results with ADT+ARAT in dn-mCSPC patients but not with ADT+docetaxel. Based on these findings, SPOP status could serve as a prognostic biomarker that directs the choice of therapy for dn-mCSPC.

Reference: annalsofoncology.org/article/S0923-7534(22)03356-7/fulltext

Source: https://www.physiciansweekly.com/mutations-of-spop-mtspop-as-treatment-selection-biomarkers