Real-world patient (pt) characteristics, treatment patterns, and overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC): Insights by <i>PTEN</i> status.

Abstract

5096 Background: The loss of function of the tumor suppressor gene PTEN is associated with an increased risk of recurrence and poor clinical outcomes in advanced prostate cancer (PC). Current understanding of PTEN prevalence and pt characteristics, treatment patterns, and survival outcomes by PTEN status in mHSPC is limited. Methods: This cohort study used retrospective longitudinal data from the US-based deidentified Flatiron Health-Foundation Medicine mPC clinicogenomic database. Male pts diagnosed (dx) with mHSPC between January 1, 2018, and March 31, 2024, who underwent comprehensive genomic profiling of a solid tumor specimen were included. Pts with PTEN alterations were classified as PTEN -homs del (homozygous deletion, defined as a copy number variant [CNV]=0) or PTEN -mut (CNV=1, pathological short variant alterations or rearrangements). Pts without PTEN alterations identified were classified as PTEN -nonaltered. Pt characteristics and treatment patterns were descriptively analyzed. Kaplan-Meier survival probabilities for real-world overall survival (rwOS; unadjusted) were estimated by PTEN status ( PTEN -homs del, PTEN -mut, and PTEN -nonaltered). Results: Of 1630 included pts, 39.8% had tumors with PTEN alterations ( PTEN -homs del, 23.2%; PTEN -mut, 16.6%). Overall, pts were predominantly non-Hispanic White with a mean (SD) age of 69 (9.1) years at mHSPC dx. At initial dx, 66.7% presented with a Gleason score of 8 to 10, and 68.1% had de novo metastatic disease. Median (IQR) prostate-specific antigen level (ng/mL) at metastatic diagnosis was lower in PTEN -homs del (47 [9-193]) and PTEN -mut (42 [11-157]) mHSPC relative to PTEN -nonaltered (68 [15-337]) mHSPC. BRCA mutations were less frequent in PTEN -homs del (6.1%) tumors relative to PTEN -mut (9.6%) and PTEN -nonaltered (10.3%) tumors. All other pt characteristics were generally similar across PTEN groups. The most common first-line treatments across all PTEN groups were ADT alone and ARPI ± ADT. Median (95% CI) rwOS (months) was 29.0 (24.1-33.6) in PTEN -homs del, 32.7 (27.8-37.9) in PTEN -mut, and 42.3 (38.7-46.0) in PTEN -nonaltered mHSPC groups. Pts with PTEN alterations tended to have lower landmark survival probabilities than pts without PTEN alterations (Table). Conclusions: Among pts with mHSPC, worse survival was observed in pts with tumors harboring PTEN alterations relative to pts without PTEN tumor alterations, despite similar pt characteristics and treatment patterns across PTEN groups. rwOS probability, % (95% CI) PTEN -homs del (n=378) PTEN -mut (n=271) PTEN -nonaltered (n=981) 12 month 81.6 (76.0-87.6) 83.9 (77.9-90.4) 90.7 (88.2-93.4) 24 month 56.8 (50.6-63.7) 64.4 (57.5-72.0) 73.8 (70.3-77.4)