PAM50 HER2-enriched/ERBB2-high (HER2-E/ERBB2H) biomarker to predict response and survival following lapatinib (L) alone or in combination with trastuzumab (T) in HER2+ T-refractory metastatic breast cancer (BC): A correlative analysis of the EGF104900 phase III trial.

1025Background: In HER2+ BC, HER2-E subtype with high ERBB2 mRNA expression (HER2-E/ERBB2H) is better associated with response following neoadjuvant L and T without chemotherapy than either variable alone (ASCO2018 submitted). Here, we evaluated the ability of this combined biomarker to predict response and survival following anti-HER2 therapy alone in T-refractory HER2+ BC. Methods: EGF104900 randomized 296 women with HER2+ advanced BC who experienced progression on prior T-containing regimens to receive either L alone or L+T. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR) and clinical benefit rate (CBR). The expression of 50 PAM50 genes was evaluated from FFPE tumors using an nCounter. A pre-defined HER2-E/ERBB2H definition was applied blinded from clinical data. Multivariable analyses were used to test the association of the HER2-E/ERBB2H variable with PFS, OS, ORR and CBR. Interaction tests between the biomarker...