Johnston SRD, et al. - Researchers performed the ALTERNATIVE study to evaluate the efficacy and safety of dual HER2 blockade plus aromatase inhibitor (AI) in postmenopausal women with HER2-positive/HR-positive metastatic breast cancer (MBC) who received prior endocrine therapy (ET) and prior neo(adjuvant)/first-line trastuzumab (TRAS) plus chemotherapy. Dual HER2 blockade with LAP + TRAS + AI vs TRAS + AI demonstrated a higher progression-free survival benefit in patients with HER2-positive/HR-positive MBC. For this patient population, this combination proved an effective and safe chemotherapy-sparing alternative treatment regimen.

Methods

• Researchers randomized patients (1:1:1) to receive lapatinib (LAP) + TRAS + AI, TRAS + AI, or LAP + AI.
• They excluded patients for whom chemotherapy was intended.
• Progression-free survival (PFS; investigator assessed) with LAP + TRAS + AI vs TRAS + AI was observed as the primary end point.
• PFS (comparison of other arms), overall survival, overall response rate, clinical benefit rate, and safety were the secondary end points.

Results

• This analysis included 355 patients: LAP + TRAS + AI (n = 120), TRAS + AI (n = 117), and LAP + AI (n = 118).
• Baseline characteristics were balanced.
• The study met its primary end point; LAP + TRAS + AI vs TRAS + AI indicated superior PFS (median PFS, 11 v 5.7 months; hazard ratio, 0.62; 95% CI, 0.45 to 0.88; P=.0064).
• Predefined subgroups indicated consistent PFS benefit.
• LAP + TRAS + AI was also superior in terms of overall response rate, clinical benefit rate, and overall survival.
• The median PFS with LAP + AI vs TRAS + AI was 8.3 vs 5.7 months (hazard ratio, 0.71; 95% CI, 0.51 to 0.98; P=.0361).
• With LAP + TRAS + AI, TRAS + AI, and LAP + AI, common adverse events (AEs; ≥ 15%) were diarrhea (69%, 9%, and 51%, respectively), rash (36%, 2%, and 28%, respectively), nausea (22%, 9%, and 22%, respectively), and paronychia (30%, 0%, and 15%, respectively), mostly grade 1 or 2.
• Across the three groups, serious AEs were reported similarly.
• AEs leading to discontinuation were lower with LAP + TRAS + AI.