Real-world outcomes in metastatic prostate cancer patients with ctDNA-detected <i>SPOP</i> mutations.

Abstract

110 Background: Comprehensive genomic profiling (CGP) is recommended for patients (pts) with metastatic prostate cancer (mPC) to inform therapy. ctDNA analysis provides rapid results with high concordance to tissue-based CGP avoiding the need for invasive biopsy. SPOP mutations ( SPOP+ ) define a novel group of mPC enriched in black pts. Tissue-based data suggests a subset of pts with SPOP+ mPC have improved outcomes with hormonal therapy and may not require intensified treatments. This study examined outcomes for mPC pts following ctDNA-detected SPOP mutations by race. Methods: Real-world (rw) data was sourced from GuardantINFORM from 2014 to September 2024. GuardantINFORM is comprised of aggregated commercial payer health claims and de-identified records from pts with clinical ctDNA testing via Guardant360 (G360). Index date was defined as the first metastatic claim post-mPC diagnosis and baseline period as the six months prior to the index date. Adult mPC pts with &gt;2 mPC claims in the baseline period were analyzed. Demographics and rw first-line outcomes (rw time to next treatment (rwTTNT) and rw overall survival (rwOS), months) in both unmatched and propensity score matched and weighted SPOP + vs. SPOP- were assessed. A subgroup analysis was also conducted by stratifying by the two main racial groups, white and black. Results: SPOP mutations were observed in 2.6% of pts meeting inclusion criteria (346/13283). 346 SPOP+ mPC pts were included as cases, of which 205 (59%) were White, 90 (26%) Black, and 51 (15%) other/unknown race; 43% had prior ADT use (n=151) and the median age was 72 years (range: 45-84). A larger proportion of black pts were in the SPOP + cohort compared to SPOP - (21.8% vs. 14.9%) with other demographics similar between cohorts (age, non-Black race, line of therapy, prior ADT use). In unmatched analyses, SPOP+ had numerically similar median rwTTNT and shortened median rwOS compared to SPOP -, although not significant [rwTTNT: SPOP + 12.7 (10.1-14.3) vs. SPOP - 12.4 (11.8-13.0); p=0.86; rwOS: SPOP + 18.3 (15.2-25.8) vs. SPOP - 21.9 (20.7-22.7); p=0.33]. Upon stratifying by race in matched and weighted cohorts, SPOP + black pts had numerically improved median rwTTNT and median rwOS compared to SPOP + white pts, yet not significant [rwTTNT: Black- SPOP + 13.7 (9.2-NR) vs. White- SPOP + 12.4 (8.3-14.5); p=0.66; rwOS: Black- SPOP + 18.9 (14.7-NR) vs. White- SPOP + 17.1 (13.1-29.1); p=0.38]. Conclusions: This data supports ctDNA use for detecting S POP mutation status in mPC. SPOP + may impact rwTTNT and rwOS among black pts. Further modeling of real-world matched cohorts and additional studies in clinical cohorts are needed to continue to assess the impact of SPOP + on patient outcomes.