Abstract PD18-02: Adjuvant Paclitaxel and Trastuzumab Trial (APT) for Node-Negative, Human Epidermal Growth Factor Receptor 2–Positive (HER2+) Breast Cancer: final 10-year analysis
Authors: Tolaney Sara , Tarantino Paolo , Graham Noah , Tayob Nabihah , Dang Chau T , Yardley Denise , Moy Beverly , Marcom Paul K. , Albain Kathy S. , Rugo Hope , Ellis Matthew , Shapira Iuliana , Wolff Antonio C. , Carey Lisa , Barroso-Sousa Romualdo , DeMeo Michelle K. , DiLullo Molly K. , Partridge Ann , Waks Adrienne , Hudis Clifford , Krop Ian , Burstein Harold , Prat Aleix , Winer Eric 
Published: March 2023

Abstract
Background: The APT trial evaluated the activity of adjuvant paclitaxel and trastuzumab (TH) among patients with small, node negative HER2+ breast cancer. This regimen showed a 7-year invasive disease-free survival (iDFS) of 93%, a recurrence-free interval (RFI) of 97.5% with only four (1.0%) distant recurrences, and a 7-year overall survival (OS) of 95%. In this end-of-study analysis, we report the survival outcomes at 10 years and assess the role of HER2DX testing in predicting long-term outcomes with adjuvant TH.
Methods: APT was a single-arm multicenter investigator-initiated phase II study in which patients with HER2+ breast cancer with tumors ≤3 cm and negative nodes (one single micrometastatic node allowed) received IV weekly paclitaxel (80 mg/m2) with IV weekly trastuzumab for 12 weeks, followed by IV trastuzumab for 9 months. The primary endpoint was 3-year iDFS. Here we report 10-year iDFS, RFI, breast cancer–specific survival (BCSS) and OS. In an exploratory analysis, the risk of recurrence was evaluated with the HER2DX genomic assay.
Results: A total of 410 patients were enrolled from October 2007 to September 2010, of which 406 started the study treatment and were included in the intent to treat analysis. Median age at enrollment was 55 years (range, 24 to 85 years), and most patients (67%) had hormone receptor (HR)-positive disease. Fifty percent of patients had tumors 1.0 cm or smaller and only 9% of patients had tumors between 2 cm to 3 cm. Mean tumor size was 1.1 cm. After a median follow-up of 10.2 years (122 months), 36 iDFS events were observed, consistent with a 10-year iDFS of 89.7% (95% CI, 86.3%-93.1%). Ten-year iDFS was 90.2% (95% CI, 86.3%-94.3%) and 88.5% (95% CI, 82.4%-95.1%) for patients with HR-positive and HR-negative tumors at baseline, respectively. 10-year RFI was 96.8% (95% CI, 95.0%-98.7%), 10-year OS was 94.2% (95% CI, 91.6%-96.8%) and 10-year BCSS was 99.1% (95% CI, 98.1%-100.0%). Of the iDFS events observed in the trial, 6 were non-breast cancer related deaths and 9 were contralateral tumors, all but one locally found to be HER2-negative upon biopsy (Table 1). Among patients experiencing an iDFS event, 7 patients (1.7%) had distant recurrences, including 1 with a T2 tumor, 3 with a T1c tumor and 3 with a T1b tumor. At baseline, 6 of them had HR-positive disease, 1 had HR-negative disease, and 6 had high-grade disease. Upon biopsy of metastatic lesions, 5 of the 7 distant recurrences were locally found to be HER2+, 1 was HER2-negative and 1 had unknown HER2 status. HER2DX testing was conducted on available baseline archival tumor tissue and analyses of patients’ survival outcomes based on the HER2DX score will be presented.
Conclusion: After 10 years of follow-up, adjuvant TH confirmed excellent long-term outcomes for small, node-negative HER2+ breast cancer, with a 10-year RFI of 96.8% and a 10-year BCSS of 99.1%.
Table 1: iDFS events with adjuvant paclitaxel plus trastuzumab after 10.2 years of follow up
Citation Format: Sara Tolaney, Paolo Tarantino, Noah Graham, Nabihah Tayob, Chau T Dang, Denise Yardley, Beverly Moy, Paul K. Marcom, Kathy S. Albain, Hope Rugo, Matthew Ellis, Iuliana Shapira, Antonio C. Wolff, Lisa Carey, Romualdo Barroso-Sousa, Michelle K. DeMeo, Molly K. DiLullo, Ann Partridge, Adrienne Waks, Clifford Hudis, Ian Krop, Harold Burstein, Aleix Prat, Eric Winer. Adjuvant Paclitaxel and Trastuzumab Trial (APT) for Node-Negative, Human Epidermal Growth Factor Receptor 2–Positive (HER2+) Breast Cancer: final 10-year analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD18-02.