Article
作者: Faggen, Meredith ; Marcom, P. Kelly ; Partridge, Ann H. ; Russo, Leila ; Krop, Ian E. ; Ardman, Blair ; DiLullo, Molly ; Schneider, Bryan ; Burstein, Harold J. ; Dell'Orto, Patrizia ; Constantine, Michael ; Viale, Giuseppe ; Winer, Eric P. ; Mittendorf, Elizabeth A. ; Prat, Aleix ; Zuckerman, Dan ; Tayob, Nabihah ; Tarantino, Paolo ; Kirkup, Christian ; Dang, Chau ; Newhouse, Daniel J. ; DeFusco, Patricia ; Reeder-Hayes, Katherine ; Liu, Minetta C. ; Valero, Vicente ; Rugo, Hope S. ; Curigliano, Giuseppe ; Wolff, Antonio C. ; Waks, Adrienne G. ; Tung, Nadine ; Cheng, Kit ; Krause, Emma ; Hart, Lowell ; Forero-Torres, Andres ; Weckstein, Douglas ; Ruddy, Kathryn J. ; Hui, Winnie ; DeMeo, Michelle ; Kurt, Busem Binboğa ; Yardley, Denise A. ; Albain, Kathy ; Pohlmann, Paula R. ; Tolaney, Sara M. ; Jankowitz, Rachel C. ; Zheng, Yue ; Abramson, Vandana ; Garrett, Audrey Merrill ; Gadi, Vijayakrishna K. ; Van Poznak, Catherine ; Mulvey, Therese ; Nanda, Rita ; Rimawi, Mothaffar ; Villacampa, Guillermo ; Barroso-Sousa, Romualdo ; Bose, Ron ; Isakoff, Steven J. ; Ramaswamy, Bhuvaneswari
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.