Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor–Positive Metastatic Breast Cancer: ALTERNATIVE

PurposeHuman epidermal growth factor receptor 2 (HER2) targeting plus endocrine therapy (ET) improved clinical benefit in HER2-positive, hormone receptor (HR)–positive metastatic breast cancer (MBC) versus ET alone. Dual HER2 blockade enhances clinical benefit versus single HER2 blockade. The ALTERNATIVE study evaluated the efficacy and safety of dual HER2 blockade plus aromatase inhibitor (AI) in postmenopausal women with HER2-positive/HR-positive MBC who received prior ET and prior neo(adjuvant)/first-line trastuzumab (TRAS) plus chemotherapy.MethodsPatients were randomly assigned (1:1:1) to receive lapatinib (LAP) + TRAS + AI, TRAS + AI, or LAP + AI. Patients for whom chemotherapy was intended were excluded. The primary end point was progression-free survival (PFS; investigator assessed) with LAP + TRAS + AI versus TRAS + AI. Secondary end points were PFS (comparison of other arms), overall survival, overall response rate, clinical benefit rate, and safety.ResultsThree hundred fifty-five patients were ...