Relevance of serum HER2 extracellular domain (sECD) in EGF30008, a study of letrozole ± lapatinib in patients (pts) with hormone-receptor positive (HR+) metastatic breast cancer (MBC)
1019 Background: Elevated baseline sECD (BsECD) correlates weakly with HER2 overexpression (HER2+). HR+ MBC. Lapatinib benefit was reported in pts with HER2+ tumors irrespective of BsECD status; BsECD status did not predict benefit for HER2- negative (HER2-ve) tumors. sECD levels and their predictive and prognostic value for progression-free survival (PFS) were further examined in a randomized, phase III trial of letrozole ± lapatinib. Methods: Pts (n=1286) with HR+ MBC were randomized to letrozole with placebo (P) or lapatinib (L). HER2 status was evaluated by FISH or IHC in archived tissue. sECD was measured by ELISA at baseline (n=1102 available samples), and every 4 wk. Pts were considered sECD+ if serum sECD was >15 ng/ml. Results: BsECD was positive in 14% (125/894) and 42% (87/208) of pts with HER2-ve and HER2+ tumors, respectively. Correlation between BsECD and FISH was weak but significant in HER2+ pts (R=0.35, p<0.0001) but not in HER2-ve pts (R=0.03, p=0.362). Unlike for HER2+ tumors, BsECD+ did not predict benefit in PFS from L in pts with HER2-ve tumors. HR: Hazard Ratio In pts with HER2- ve tumors, median ECD levels were stable in the P arm but increased slightly (4 ng/mL) in the L arm. In the HER2+ group, median levels in the P arm declined (3.5 ng/mL) but increased at 4 wk in L arm (3.4 ng/mL) and were stable thereafter. Conversion from sECD-ve to sECD+ was observed in both arms but did not correlate with outcome or provide predictive value. Data related to ECD status conversion will be reported. Conclusions: BsECD+ status correlates with HER2+ tumor status and may predict L benefit but BsECD+ status did not predict benefit in pts with HER2-ve tumors. On therapy changes in median sECD were small. Conversion from BsECD-ve to sECD+ did not predict L benefit and we could not confirm that evaluation of on treatment ECD status may help treatment decision. [Table: see text] [Table: see text]