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).

Shoichiro Ohtani,Masahiro Takada,Shinji Ohno,Toshimi Takano,Kenichi Sakurai,Masakazu Toi,Kentaro Inoue ,Katsumasa Kuroi,Tomomi Fujisawa,Satoshi Morita,Nobuyasu Suganuma,Nobuto Yamamoto ,Kenjiro Aogi,Tomoyuki Aruga,Eriko Tokunaga,Hideo Shigematsu,Hiroko Bando,Norikazu Masuda,Hironori Haga,Hiroji Iwata

doi:10.3390/cancers13164008

Abstract

Simple SummaryWe 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.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.

Highlights

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is an aggressive phenotype associated with a poor prognosis [1]
All patients (n = 212) who participated in the Neo-LaTH study were included in the present follow-up study; 1 patient withdrew during the follow-up period, this patient provided consent to use her data on survival from randomization to the date of consent withdrawal, and these data were included in the analysis (Figure S1)
In this long-term follow-up study of patients receiving neoadjuvant dual anti-HER2 therapy with lapatinib and trastuzumab combined with weekly paclitaxel, we found the following main findings: The 5-year disease-free survival (DFS), DDFS, and overall survival (OS) rates were approximately 90%

Summary

Introduction

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is an aggressive phenotype associated with a poor prognosis [1]. With development of HER2-targeted therapy, such as the humanized monoclonal antibody trastuzumab, the prognosis of HER2-positive breast cancer has markedly improved [2,3,4,5,6]. In the neoadjuvant setting for early-stage, HER2-positive breast cancer, several studies have reported increased efficacy by adding dual HER2 blockade therapy to chemotherapy [8,9,10]. In the NeoALTTO study [12], a combination of lapatinib, which is a small-molecule tyrosine kinase inhibitor, and trastuzumab was examined. Both of these studies reported a significantly increased pathological complete response (pCR) rate

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