Prognostic and genomic implications of HER2 expression in metastatic prostate cancer.

Abstract

252 Background: Evidence regarding the prevalence and clinical or biological relevance of Her2 expression in metastatic prostate cancer (mPC) remains limited. Methods: 52 patients (pts) with mPC (48 mCPHS, 4 mCRPC) were retrospectively analyzed. HER2 IHC was performed on FFPE primary and/or metastatic samples using the Dako HercepTest (Agilent platform), scored per gastric/solid-tumor criteria (0, 1+, 2+, 3+). Clinical and laboratory parameters were correlated with HER2 status (0 vs ≥1+). Genomic profiling included TP53, RB1, PTEN, and BRCA1/2. Progression-free survival (PFS) was defined from 1st-line therapy start to progression or death; overall survival (OS) from metastatic diagnosis. Survival was estimated by Kaplan–Meier and compared by log-rank test. Results: HER2 ≥1+ was observed in 59.6% of pts (IHC 1+ = 17%, 2+ = 21%, 3+ = 21%). Baseline characteristics are summarized in Table 1. HER2 0 tumors showed numerically higher rates of adverse clinical features, including ISUP 5 (50% vs 26%), ECOG ≥2 (21% vs 11%), visceral metastases (29% vs 16%), elevated LDH (43% vs 26%), and high-volume disease (57% vs 53%), none reached statistical significance (all p > 0.1). Molecularly, HER2 0 tumors were enriched for BRCA1/2 (24% vs 11%, p = 0.18), TP53 (58% vs 29%, p = 0.11), RB1 (42% vs 14%, p = 0.09), and PTEN (37% vs 7%, p = 0.04) alterations. The only TP53/RB1/PTEN triple-hit occurred in a HER2 0 tumor. No ERBB2 mutations were detected. Median PFS with 1st-line therapy in M1-HSPC pts was numerically shorter for HER2 0 versus HER2 ≥1+ (11.2 vs 16.8 months; HR 1.42, p = 0.18), with consistent trends across chemotherapy and non-chemotherapy regimens. OS was immature (median follow-up 17 months; 26% deaths). None of the pts received HER2-directed ADCs. At the time of submission, genomic results were available for 22 pts; sequencing of 20 additional cases is ongoing, while 10 were not evaluable due to tissue limitations. Conclusions: HER2 expression (IHC ≥1+) was present in approximately 60% of mPC cases. Although not statistically significant, HER2 0 tumors showed enrichment in TP53/RB1/PTEN/BRCA1/2 alterations and a trend toward shorter PFS, consistent across treatment subgroups. These findings suggest that loss of HER2 expression may define a genomically adverse subset of mPC that warrants further validation. Patient characteristics. Age, years – median (range) 69 (51–91) ECOG PS – n(%)  0 20 (38.5)  ≥1 32 (61.5) HER2 expression (IHC) – n(%)  0 21 (40.4)  1+ 9 (17.3)  2+ 11 (21.2)  3+ 11 (21.2) HER2 tested Prostate Lymph node Extranodal metastasis Primary + metastatic site 46 (88.5%)1 (1.9%)2 (3.8%)3 (5.8%) Genomic alterations – n(%)  BRCA2 4/22 (18%)  BRCA1 1/22 (4.5%) Triple hit (PTEN+p53+RB1) 1/22 (4.5%) First metastatic presentation – n(%)  mHSPC recurrent LV 5 (9.6)  mHSPC de novo LV 13 (25.0)  mHSPC recurrent HV 1 (1.9)  mHSPC de novo HV 29 (55.8)  mCRPC 4 (7.7) Sites of disease – n(%)  Bone 41 (78.8)  Lymph nodes 38 (73.1)  Lung 10 (19.2)