Abstract
182 Background: IPATential150 is a randomized trial comparing Ipat + Abi vs placebo + Abi in patients (pts) with 1L mCRPC (NCT03072238). We evaluated the potential associations between PTEN loss, genomic alterations, and country of enrollment (East Asian [EAS] vs non-EAS). Methods: Before randomization, tumor samples (archival > 90%) were centrally tested for PTEN loss by VENTANA PTEN (SP218) immunohistochemistry (IHC) assay (N = 1101). Tumor genetic alterations were profiled by Foundation Medicine FoundationOne CDx (F1CDx) NGS assay (n = 735). Results: Of 1101 pts enrolled, 521 (47%) had PTEN loss by IHC. An overall 76% agreement was observed between PTEN IHC and F1CDx. TMPRSS2 fusion, alterations in TP53 and PTEN were most frequent (28%-32%). Alterations in PIK3CA, SPOP, APC, MYC, RAD21, and genes involved in DNA damage repair, including BRCA2, CDK12, ATM, had a 5%-8% prevalence. PTEN loss (IHC) tended to co-occur with genetic alterations in TP53 and TMPRSS2. The prevalence of PTEN loss in EAS vs non-EAS pts was 35% vs 50% by IHC and 15% vs 31% by F1CDx. Alterations in CDK12, BRCA2, SPOP, and MYC were more prevalent in EAS pts, whereas alterations in TMPRSS2, PTEN, and TP53 were more prevalent in non-EAS pts. Conclusions: This analysis reveals molecular heterogeneity in prostate cancer and association between potentially actionable targets. It also suggests that EAS pts with mCRPC have a genetic profile that may be at least quantitatively different from non-EAS pts. Clinical trial information: NCT03072238. [Table: see text]
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