Long-Term Outcomes of a Randomized Study of Neoadjuvant Induction Dual HER2 Blockade with Trastuzumab and Lapatinib Followed by Weekly Paclitaxel Plus Dual HER2 Blockade for HER2-Positive Primary Breast Cancer (Neo-Lath Study)

SIMPLE SUMMARY: We conducted the Neo-LaTH study in which patients with HER2-positive breast cancer were randomized to different lengths of neoadjuvant induction anti-HER2 therapy with lapatinib and trastuzumab followed by weekly paclitaxel plus anti-HER2 therapy, and in estrogen receptor-positive patients, with or without concurrent endocrine therapy. Here, we report the survival outcomes. The duration of neoadjuvant induction therapy and/or the addition of endocrine therapy at randomization did not affect the pathological complete response (CpCR) rate after neoadjuvant treatment and long-term outcomes. The 5-year disease-free survival rate was significantly higher in patients who had CpCR plus ypN0 after neoadjuvant treatment than in those who did not (91.7% vs. 85.1%; p = 0.0387). The stratified analysis showed better survival outcomes in CpCRypN0 patients than non-CpCRypN0 patients, regardless of use of adjuvant anthracycline therapy. Favorable survival outcomes, regardless of adjuvant anthracycline, were particularly noted in patients with small size and clinically node-negative tumors. ABSTRACT: We conducted the Neo-LaTH study in which patients were randomized to different lengths of neoadjuvant induction anti-HER2 therapy with lapatinib and trastuzumab followed by weekly paclitaxel plus the anti-HER2 therapy, and in estrogen receptor (ER)-positive patients, with or without concurrent endocrine therapy. The use of endocrine therapy did not affect the response; comprehensive pathological complete response (CpCR) plus ypN0 rate was 57.6% and 30.3% in ER-negative and ER-positive patients, respectively. After surgery, patients received an anthracycline-based regimen based on physician’s choice, followed by trastuzumab for 1 year, and in ER-positive patients, endocrine therapy for 5 years. Here, we report the 5-year survival outcomes. Among the followed-up patients (n = 212), the 5-year disease-free survival (DFS), distant DFS, and overall survival rates were 87.8% [95% confidence interval (CI), 82.5–91.6%], 93.7% (95% CI, 89.3–96.3%), and 95.6% (95% CI, 91.7–97.7%), respectively, with no difference between ER-negative and ER-positive patients. The 5-year DFS rate was significantly higher in patients who had a CpCR plus ypN0 after neoadjuvant treatment than in those who did not (91.7% vs. 85.1%; p = 0.0387). The stratified analysis showed better survival outcomes in patients who had CpCRypN0 than in those who did not after neoadjuvant treatment, regardless of use of adjuvant anthracycline therapy.