Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT
Authors: Tarantino Paolo , Tayob Nabihah , Villacampa Guillermo , Dang Chau , Yardley Denise A. , Isakoff Steven J. , Valero Vicente , Faggen Meredith , Mulvey Therese , Bose Ron , Weckstein Douglas , Wolff Antonio C. , Reeder-Hayes Katherine , Rugo Hope S. , Ramaswamy Bhuvaneswari , Zuckerman Dan , Hart Lowell , Gadi Vijayakrishna K. , Constantine Michael , Cheng Kit , Garrett Audrey Merrill , Marcom P. Kelly , Albain Kathy , DeFusco Patricia , Tung Nadine , Ardman Blair , Nanda Rita , Jankowitz Rachel C. , Rimawi Mothaffar , Abramson Vandana , Pohlmann Paula R. , Van Poznak Catherine , Forero-Torres Andres , Liu Minetta C. , Ruddy Kathryn J. , Waks Adrienne G. , DeMeo Michelle , Burstein Harold J. , Partridge Ann H. , Dell'Orto Patrizia , Russo Leila , Krause Emma , Newhouse Daniel J. , Kurt Busem Binboğa , Mittendorf Elizabeth A. , Schneider Bryan , Prat Aleix , Winer Eric P. , Krop Ian E. , Tolaney Sara M. ,   on behalf of the Consortium of the TBCRC Translational Investigators, Barroso-Sousa Romualdo , Curigliano Giuseppe , DiLullo Molly , Hui Winnie , Kirkup Christian , Viale Giuseppe , Zheng Yue 
Published: June 2024

PURPOSE
Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)–positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

METHODS
In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia.

RESULTS

After a median follow-up of 5.8 years, 11 iDFS events were observed in the T-DM1 arm, consistent with a 5-year iDFS of 97.0% (95% CI, 95.2 to 98.7). At 5 years, the recurrence-free interval (RFI) was 98.3% (95% CI, 97.0 to 99.7), the overall survival was 97.8% (95% CI, 96.3 to 99.3), and the breast cancer-specific survival was 99.4% (95% CI, 98.6 to 100). Comparable iDFS was observed with T-DM1 irrespective of tumor size, hormone receptor status, centrally determined HER2 immunohistochemical score, and receipt of T-DM1 for more or less than 6 months. Although ATEMPT was not powered for this end point, the 5-year iDFS in the TH arm was 91.1%. Among patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes significantly differed according to HER2DX risk score, with better RFI (98.1%
v
81.8%, hazard ratio [HR], 0.10,
P
= .01) and iDFS (96.3%
v
81.8%, HR, 0.20,
P
= .047) among patients with HER2DX low-risk versus high-risk tumors, respectively.

CONCLUSION
Adjuvant T-DM1 for 1 year leads to outstanding long-term outcomes for patients with stage I HER2-positive breast cancer. A high HER2DX risk score predicted a higher risk of recurrence in ATEMPT.