The following is a summary of “SPOP Mutations as a Predictive Biomarker for Androgen Receptor Axis–Targeted Therapy in De Novo Metastatic Castration-Sensitive Prostate Cancer” published in the November 2022 issue of Clinical Cancer by Swami et al.
Patients with castration-sensitive metastatic prostate cancer are typically treated with docetaxel or androgen receptor axis-targeted treatments (ARAT) to intensify androgen deprivation therapy (ADT), metastatic castration-sensitive prostate cancer (mCSPC). Nonetheless, there are no readily available biomarkers to help doctors decide which therapies to use. Researchers expected that patients with de novo (dn)-mCSPC who carried SPOP mutations would benefit from ADT intensification with ARAT but not docetaxel. Between January 2011 and December 2021, investigators pulled patient-level data from a deidentified national (U.S.-based) prostate cancer clinico-genomic database.
Eligibility requirements include a diagnosis of metastatic disease within 30 days of the initial diagnosis of prostate cancer, genomic profiling of a tissue biopsy taken within 90 days of the initial diagnosis, and commencement with ARAT or docetaxel within 120 days of the initial diagnosis. Overall survival (OS) and the time it took for prostate cancer to become resistant to ADT in patients with and without SPOP mutations who had ADT intensification with ARAT or docetaxel were compared using the log-rank test and Cox proportional hazards models.
In the ARAT cohort, the presence of a SPOP mutation was linked to better overall survival (OS) (not reached vs. 27.2 months; aHR, 0.19; 95% CI, 0.05-0.79; P=0.022) and progression-free survival (PFS) (NR vs. 16.7 months; aHR, 0.20; 95% CI, 0.06-0.63; P=0.006). In the docetaxel-treated cohort, SPOP mutation status was not related to TTCRPC or OS. Patients with dn-mCSPC with a SPOP mutation had a better response to ADT plus ARAT (but not to ADT plus docetaxel) in the real world. This has the potential to be a predictive biomarker for the selection of treatment for patients with mCSPC.