Key points are not available for this paper at this time.
5091 Background: TSG-alt have been associated with poor survival in the mCRPC setting (PMID: 31061129) and in the mCSPC setting from small single institution cohorts (PMID: 34294873). However, large studies evaluating their impact on survival outcomes with ADT intensification in mCSPC setting are lacking. Herein, we evaluate the impact of TSG-alt on outcomes in a large real-world patient population with dn-mCSPC receiving ADT treatment (Rx) with ARPI or docetaxel. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine Prostate Cancer clinical-genomic database (FH-FMI CGDB), with de-identified data originating from approximately 800 US cancer clinics. Inclusion criteria: dn-mCSPC, tissue biopsy within 90 days of diagnosis, and initiation of ARPI or docetaxel + ADT within 120 days of diagnosis. Time to castration-resistance (TTCR) and overall survival (OS), indexed from metastatic diagnosis, were evaluated with Cox proportional hazards models adjusted for baseline prognostic factors (PSA, Gleason score, age, ECOG, hemoglobin, alkaline phosphatase, and albumin). OS risk intervals were left truncated to date of comprehensive genomic profiling report to adjust for immortal time bias. Results: Of 5356 pts in FH-FMI CGDB, 571 met inclusion criteria. Of these, 321 received ADT + ARPI and 250 ADT + docetaxel. Pts with pathogenic TSG alt were: 214 TP53 (37%), 154 PTEN (27%), and 37 RB1 (6%). Results are summarized in Table. Conclusions: In this real-world analysis, alt RB1 and alt TP53 had worse OS than their respective wild-type (wt) counterparts with both ARPI and docetaxel whereas alt PTEN had similar OS with ARPI and Docetaxel in dn-mCSPC pts. Based on these results, RB1 and TP53 may represent prognostic biomarkers guiding treatment selection and clinical trial enrollment in dn-mCSPC and may assist with counseling and prognostication. Table: see text
Narang et al. (Sat,) studied this question.