HER2 extracellular domain (ECD) and HER2 single nucleotide polymorphisms (SNPs) in patients treated with combination trastuzumab, lapatinib, and bevacizumab.

e22082 Background: Biomarkers associated with efficacy of HER2-directed treatments are lacking. We evaluated HER2 ECD levels and HER2 SNPs in patients treated on a clinical trial of combination trastuzumab, lapatinib, and bevacizumab. Methods: Plasma samples were obtained at baseline, 24-48 hrs post-dose, and end of cycle 1. Plasma circulating HER2 ECD was determined using ELISA, and 5 ng/mL was the defined upper limit of normal. HER2 SNPs were analyzed from genomic DNA from PBMCs for five annotated SNPs in the HER2 gene (-3444C>T, -1985 G>T, I655A A>G, P1170A C>G, rs1810132 STR C>T) using Sanger sequencing. Clinical response was defined as stable disease ≥6 months or partial response (SD≥6 months/PR). HER2 ECD levels and percent change at baseline, 24-48 hrs, and end of cycle 1 were compared for responders vs. non-responders. Response rate (RR) and time to treatment failure (TTF) were compared for patients with baseline HER2 ECD levels >5 ng/mL vs. ≤5 ng/mL. RR and TTF were also analyzed for each of the ...