Abstract

The excellent outcomes seen in patients treated with adjuvant trastuzumab emtansine (T-DM1) in the ATEMPT trial and the favorable toxicity profile associated with this agent make T-DM1 a potential therapeutic option for select patients with stage I HER2-positive breast cancer. Moreover, T-DM1 is an established adjuvant treatment for patients with HER2-positive breast cancer with the residual invasive disease after neoadjuvant therapy. Given that cardiotoxicity is the most significant adverse event of trastuzumab, which is a main molecular component of T-DM1, we conducted a sub-analysis of the ATEMPT trial to determine the cardiac safety of adjuvant T-DM1. In this analysis, the incidence of grade 3–4 left ventricular systolic dysfunction (LVSD) in T-DM1 or trastuzumab plus paclitaxel arms were respectively 0.8 and 1.8%. In addition, three (0.8%) patients in the T-DM1 arm and six (5.3%) patients in the adjuvant paclitaxel with trastuzumab (TH) arm experienced a significant asymptomatic left ventricular ejection fraction (LVEF) decline that per-protocol required holding T-DM1 or trastuzumab. All patients with available follow-up data experienced full resolution of cardiac symptoms and LVEF normalization. Furthermore, we performed an exploratory analysis to assess the relationship between age, baseline LVEF, and body mass index with cardiac outcomes. No significant association between these baseline characteristics and the incidence of significant asymptomatic LVEF decline or symptomatic LVSD was identified. The low incidence of significant cardiac adverse events in this population during therapy with adjuvant T-DM1 suggests that studies on the cost-effectiveness of cardiac monitoring during adjuvant therapy using anthracycline-free regimens are needed.

Clinical Trial Registration: ClinicalTrials.gov, NCT01853748

Details

Title
Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial
Author
Barroso-Sousa Romualdo 1 ; Tarantino, Paolo 2   VIAFID ORCID Logo  ; Tayob Nabihah 3 ; Dang Chau 4   VIAFID ORCID Logo  ; Yardley, Denise A 5 ; Isakoff, Steven J 6 ; Valero, Vicente 7 ; Faggen Meredith 8 ; Mulvey, Therese 6 ; Bose, Ron 9 ; Hu Jiani 8 ; Weckstein Douglas 8 ; Wolff, Antonio C 10   VIAFID ORCID Logo  ; Reeder-Hayes, Katherine 11 ; Rugo, Hope S 12 ; Bhuvaneswari, Ramaswamy 13   VIAFID ORCID Logo  ; Zuckerman, Dan 14 ; Hart, Lowell 15 ; Gadi, Vijayakrishna K 16 ; Constantine, Michael 8 ; Cheng, Kit 17 ; Briccetti Frederick 8 ; Schneider, Bryan 18 ; Garrett, Audrey Merrill 19 ; Marcom Kelly 20   VIAFID ORCID Logo  ; Albain, Kathy 21 ; DeFusco, Patricia 22 ; Tung, Nadine 23 ; Ardman Blair 24 ; Nanda, Rita 25   VIAFID ORCID Logo  ; Jankowitz, Rachel C 26   VIAFID ORCID Logo  ; Rimawi Mothaffar 27   VIAFID ORCID Logo  ; Abramson Vandana 28 ; Pohlmann, Paula R 29   VIAFID ORCID Logo  ; Van Poznak Catherine 30   VIAFID ORCID Logo  ; Forero-Torres, Andres 31 ; Liu, Minetta 32   VIAFID ORCID Logo  ; Ruddy, Kathryn J 32   VIAFID ORCID Logo  ; Zheng, Yue 8   VIAFID ORCID Logo  ; Rosenberg, Shoshana M 33 ; Gelber, Richard D 3 ; Trippa Lorenzo 3 ; Barry, William 8 ; DeMeo, Michelle 8 ; Burstein, Harold 3 ; Partridge, Ann 3   VIAFID ORCID Logo  ; Winer, Eric P 3   VIAFID ORCID Logo  ; Krop, Ian 3   VIAFID ORCID Logo  ; Tolaney, Sara M 3   VIAFID ORCID Logo 

1  Oncology Center, Hospital Sírio-Libanês Brasília, Brasília, Brazil 
2  European Institute of Oncology IRCCS, Milan, Italy (GRID:grid.15667.33) (ISNI:0000 0004 1757 0843); University of Milan, Milan, Italy (GRID:grid.4708.b) (ISNI:0000 0004 1757 2822); Dana-Farber Cancer Institute, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
3  Dana-Farber Cancer Institute, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
4  Memorial Sloan Kettering Cancer Center, New York, USA (GRID:grid.51462.34) (ISNI:0000 0001 2171 9952) 
5  Sarah Cannon Research Institute and Tennessee Oncology, Nashville, USA (GRID:grid.492963.3) (ISNI:0000 0004 0480 9560) 
6  Massachusetts General Hospital, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
7  The University of Texas MD Anderson Cancer Center, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
8  Dana-Farber Cancer Institute, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910) 
9  Washington University, St Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002) 
10  Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, USA (GRID:grid.65499.37) 
11  UNC Chapel Hill, Chapel Hill, USA (GRID:grid.10698.36) (ISNI:0000000122483208) 
12  UCSF, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
13  OSU Comprehensive Cancer Center, Columbus, USA (GRID:grid.261331.4) (ISNI:0000 0001 2285 7943) 
14  St Luke’s Mountain States Tumor Institute, Boise, USA (GRID:grid.429388.c) (ISNI:0000 0004 0446 0952) 
15  Wake Forest Baptist Health, Winston-Salem, USA (GRID:grid.412860.9) (ISNI:0000 0004 0459 1231) 
16  University of Washington, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); Vijayakrishna K. Gadi’s current affiliation is University of Illinois at Chicago, Chicago, USA (GRID:grid.185648.6) (ISNI:0000 0001 2175 0319) 
17  North Shore-LIJ Cancer Institute, Lake Success, USA (GRID:grid.416477.7) (ISNI:0000 0001 2168 3646) 
18  IU School of Medicine, Indianapolis, USA (GRID:grid.257413.6) (ISNI:0000 0001 2287 3919) 
19  Northern Light Cancer Care, Brewer, USA (GRID:grid.257413.6) 
20  Duke University, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961) 
21  Loyola University Medical Center, Maywood, USA (GRID:grid.411451.4) (ISNI:0000 0001 2215 0876) 
22  Hartford Healthcare Cancer Institute, Hartford, USA (GRID:grid.277313.3) (ISNI:0000 0001 0626 2712) 
23  Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Beth Israel Deaconess Medical Center, Boston, USA (GRID:grid.239395.7) (ISNI:0000 0000 9011 8547) 
24  Lowell General Hospital, Lowell, USA (GRID:grid.461527.3) (ISNI:0000 0004 0383 4123) 
25  The University of Chicago, Chicago, USA (GRID:grid.170205.1) (ISNI:0000 0004 1936 7822) 
26  Abramsom Cancer Center, University of Pennsylvania, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
27  Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, USA (GRID:grid.39382.33) (ISNI:0000 0001 2160 926X) 
28  Vanderbilt-Ingram Cancer Center, Nashville, USA (GRID:grid.412807.8) (ISNI:0000 0004 1936 9916) 
29  Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, USA (GRID:grid.411667.3) (ISNI:0000 0001 2186 0438) 
30  Rogel Cancer Center, University of Michigan, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
31  Kirklin UAB Hematology Oncology, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000000106344187) 
32  Mayo Clinic, Rochester, USA (GRID:grid.66875.3a) (ISNI:0000 0004 0459 167X) 
33  Dana-Farber Cancer Institute, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Weill Cornell Medicine, New York, USA (GRID:grid.5386.8) (ISNI:000000041936877X) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
23744677
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41523-022-00385-2
ProQuest document ID
2629161066
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.