Lapatinib or trastuzumab with taxane therapy as first-line treatment in metastatic breast cancer (MBC): A biomarker analysis in NCIC CTG MA.31.

601 Background: Lapatinib (L) was associated with shorter progression-free survival (PFS) than trastuzumab (T) when combined with a taxane (Tax) as first line therapy for HER2+ MBC. We report the effects of 6 centrally reviewed biomarkers on efficacy. Methods: MA.31 accrued 652 patients with locally assessed HER2+ tumors of which 537 (82%) were HER2+ by central review. Protocol-mandated immunohistochemistry was conducted centrally for ER, PR, Ki67, EGFR, and CK5. The primary endpoint was progression free survival (PFS) defined as time from randomization to progression or death in the intention to treat (ITT) population. Stratified step-wise forward Cox models examined the multivariate (mv) effects of baseline characteristics and continuous biomarkers (% positive) on PFS in the ITT and centrally confirmed HER2+ populations. Predictive effects were investigated with cutpoints of >0% of any staining intensity for ER, PR, EGFR, CK5, and >geometric mean for Ki67 for both populations. Results: Assessments were ...