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
Original language | English (US) |
---|---|
Article number | 18 |
Journal | npj Breast Cancer |
Volume | 8 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2022 |
ASJC Scopus subject areas
- Oncology
- Radiology Nuclear Medicine and imaging
- Pharmacology (medical)
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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. / Barroso-Sousa, Romualdo; Tarantino, Paolo; Tayob, Nabihah; Dang, Chau; Yardley, Denise A.; Isakoff, Steven J.; Valero, Vicente; Faggen, Meredith; Mulvey, Therese; Bose, Ron; Hu, Jiani; Weckstein, Douglas; Wolff, Antonio C.; Reeder-Hayes, Katherine; Rugo, Hope S.; Ramaswamy, Bhuvaneswari; Zuckerman, Dan; Hart, Lowell; Gadi, Vijayakrishna K.; Constantine, Michael; Cheng, Kit; Briccetti, Frederick; Schneider, Bryan; Garrett, Audrey Merrill; Marcom, 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; Ruddy, Kathryn J.; Zheng, Yue; Rosenberg, Shoshana M.; Gelber, Richard D.; Trippa, Lorenzo; Barry, William; DeMeo, Michelle; Burstein, Harold; Partridge, Ann; Winer, Eric P.; Krop, Ian; Tolaney, Sara M.
In: npj Breast Cancer, Vol. 8, No. 1, 18, 12.2022.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033)
T2 - a randomized controlled trial
AU - Barroso-Sousa, Romualdo
AU - Tarantino, Paolo
AU - Tayob, Nabihah
AU - Dang, Chau
AU - Yardley, Denise A.
AU - Isakoff, Steven J.
AU - Valero, Vicente
AU - Faggen, Meredith
AU - Mulvey, Therese
AU - Bose, Ron
AU - Hu, Jiani
AU - Weckstein, Douglas
AU - Wolff, Antonio C.
AU - Reeder-Hayes, Katherine
AU - Rugo, Hope S.
AU - Ramaswamy, Bhuvaneswari
AU - Zuckerman, Dan
AU - Hart, Lowell
AU - Gadi, Vijayakrishna K.
AU - Constantine, Michael
AU - Cheng, Kit
AU - Briccetti, Frederick
AU - Schneider, Bryan
AU - Garrett, Audrey Merrill
AU - Marcom, Kelly
AU - Albain, Kathy
AU - DeFusco, Patricia
AU - Tung, Nadine
AU - Ardman, Blair
AU - Nanda, Rita
AU - Jankowitz, Rachel C.
AU - Rimawi, Mothaffar
AU - Abramson, Vandana
AU - Pohlmann, Paula R.
AU - Van Poznak, Catherine
AU - Forero-Torres, Andres
AU - Liu, Minetta
AU - Ruddy, Kathryn J.
AU - Zheng, Yue
AU - Rosenberg, Shoshana M.
AU - Gelber, Richard D.
AU - Trippa, Lorenzo
AU - Barry, William
AU - DeMeo, Michelle
AU - Burstein, Harold
AU - Partridge, Ann
AU - Winer, Eric P.
AU - Krop, Ian
AU - Tolaney, Sara M.
N1 - Funding Information: Supported by Genentech and the Gloria Spivak Faculty Advancement Fund (Tolaney). We are grateful for the funding support to the TBCRC from The Breast Cancer Research Foundation and Susan G. Komen. Funding Information: Romualdo Barroso-Sousa: Consulting fees (e.g., advisory boards): AstraZeneca, Eli Lilly, Libbs, Merck, Roche, Zodiac. Fees for non-CME services received directly from commercial interest or their Agents (e.g., speakers’ bureaus): Bard Access, BMS, Eli Lilly, Libbs, Merck, Novartis, Pfizer, Roche. Research funding (to institution): Roche, BMS. Travel/accommodation/expenses: Eli Lilly, Roche, Daichi Sankyo, Merck. Paolo Tarantino: Consulting or advisory role: AstraZeneca. Chau Dang. Honoraria: Puma Biotechnology, eviCore healthcare. Consulting or advisory role: Puma Biotechnology, eviCore healthcare. Research funding: Genentech/Roche, Puma Biotechnology. Denise Yardley. Consulting or advisory role: Novartis, Biotheranostics, Bristol Myers Squibb, G1 Therapeutics, Athenex, Immunomedics, Sanofi/Aventis, R-Pharm, Lilly. Speakers’ Bureau: Novartis, Genentech/Roche, Genentech/Roche. Research funding: Genentech/Roche, Novartis, MedImmune, Lilly, Medivation, Pfizer, Tesaro, Macrogenics, AbbVie, Merck, Clovis Oncology, Amgen, Biomarin, Biothera, Dana-Farber Cancer Hospital, Incyte, Innocrin Pharma, Nektar, NSABP Foundation, Odonate Therapeutics, Polyphor. Travel, accommodations, expenses: Novartis, Genentech/Roche. Steven Isakoff. Consulting or advisory role: AbbVie, OncoPep, Puma Biotechnology, Seattle Genetics, Novartis. Research funding: Genentech, PharmaMar, AbbVie, OncoPep, Merck, AstraZeneca/MedImmune, Outcomes4Me. Vicente Valero. Honoraria: Genentech/Roche, Merck, Novartis. Consulting or advisory role: Genentech/Roche, Novartis, Merck. Travel, accommodations, expenses: Genentech/Roche. Therese Mulvey. Consulting or advisory role: Outcomes4Me. Ron Bose. Consulting or advisory role: Genentech. Research funding: Puma Biotechnology. Antonio Wolff. Consulting or advisory role: Ionis Pharmaceuticals. Research funding: Biomarin, Celldex. Patents, Royalties, Other Intellectual Property: Antonio Wolff has been named as an inventor on one or more issued patents or pending patent applications related to methylation in breast cancer and has assigned his rights to JHU and participates in a royalty sharing agreement with JHU. Open payments link: https://openpaymentsdata.cms.gov/physician/357301/summary . Katherine Reeder-Hayes. Research funding: Pfizer. Hope Rugo. Honoraria: Puma Biotechnology, Mylan. Consulting or advisory role: Samsung. Research funding: Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Lilly, Genentech, Merck, Immunomedics, Odonate Therapeutics, Daiichi Sankyo, Seattle Genetics, Sermonix Pharmaceuticals, AstraZeneca. Travel, accommodations, expenses: Pfizer, Novartis, Macrogenics, Mylan, Daiichi Sankyo, AstraZeneca Spain, Merck. Open payments link: https://openpaymentsdata.cms.gov/summary . Bhuvaneswari Ramaswamy. Consulting or advisory role: Eisai. Lowell Hart. Honoraria: Novartis, Daiichi Sankyo, AstraZeneca, Seattle Genetics, G1 Therapeutics, Veracyte, Karyopharm Therapeutics. Consulting or advisory role: Genentech/Roche, Amgen, G1 Therapeutics, Merck, Seattle Genetics. Speakers’ Bureau: Bristol Myers Squibb, Lilly, Pfizer, Genentech, AstraZeneca, Novartis. Research funding: Novartis, Genentech/Roche, Bristol Myers Squibb, G1 Therapeutics, Seattle Genetics. Vijayakrishna Gadi. Stock and other ownership interests: Sengine precision medicine, Novilla, 3rdEyeBio, New Equilibrium Biosciences, Phoenix Molecular Designs. Consulting or advisory role: Seattle Genetics, Puma Biotechnology, Sanofi, Hologics. Speakers’ Bureau: Seagen, Puma, Genentech/Roche. Research funding: Agendia (to institution). Travel, accommodations, expenses: Puma, Seagen, Genentech/Roche. Open payments link: https://openpaymentsdata.cms.gov/physician/2511 . Bryan Schneider. Honoraria: Lilly, Research to Practice. Paul Marcom. Consulting or advisory role: Genentech/Roche, Immunomedics. Research funding: Novartis, Genentech/Roche, AstraZeneca, Verily, Glycomimetics, Millennium. Open payments link: https://openpaymentsdata.cms.gov/physician/237508/summary . Kathy Albain. Consulting or advisory role: Novartis, Pfizer, Myriad Genetics, Genomic Health, Agendia, Genentech/Roche. Research funding: Seattle Genetics. Other relationship: Puma Biotechnology. Nadine Tung. Research funding: AstraZeneca. Rita Nanda. Consulting or advisory role: Merck, Genentech/Roche, Pfizer, Macrogenics, Daiichi Sankyo, Athenex, Aduro Biotech, ION Pharma, Seattle Genetics, Immunomedics. Research funding: Corcept Therapeutics, Celgene, Merck, Seattle Genetics, Genentech/Roche, Odonate Therapeutics, Pfizer, AstraZeneca, AbbVie, Immunomedics. Other relationship: G1 Therapeutics. Rachel Jankowitz. Honoraria: Eisai. Consulting or advisory role: Merck. Mothaffar Rimawi. Consulting or advisory role: Macrogenics, Daiichi Sankyo, Seattle Genetics, Genentech. Research funding: Pfizer. Vandana Abramson. Employment: HCA Healthcare. Consulting or advisory role: Eisai, Daiichi Sankyo, Abbvie. Research funding: Genentech/Roche, Lilly. Paula Pohlmann. Leadership: Immunonet BioSciences. Stock and other ownership interests: Immunonet BioSciences. Honoraria: Dava Oncology, OncLive/MJH Life Sciences, Frontiers—Publisher. Consulting or advisory role: Personalized Cancer Therapy, OncoPlex Diagnostics, Immunonet BioSciences, Pfizer, HERON, Puma Biotechnology, Sirtex Medical, Caris Life Sciences, Juniper Pharmaceuticals, Bolt Biotherapeutics. Speakers’ Bureau: Genentech/Roche. Research Funding: Genentech/Roche, Fabre-Kramer, Advanced Cancer Therapeutics, Caris Centers of Excellence, Pfizer, Pieris Pharmaceuticals, Cascadian Therapeutics, Bolt Biotherapeutics, Byondis, Seagen. Patents, Royalties, Other Intellectual Property: United States Patent no. 8486413, United States Patent no. 8501417, United States Patent no. 9023362, United States Patent no. 9745377, Patent application. Catherine Van Poznak. Research funding: Bayer. Patents, Royalties, Other Intellectual Property: UpToDate. Andres Forero-Torres. Employment: Seattle Genetics. Stock and other ownership interests: Seattle Genetics. Minetta Liu. Research funding: Eisai, Seattle Genetics, Novartis, Roche/Genentech, GRAIL, Merck, Tesaro, Menarini Silicon Biosystems, Genomic Health. Travel, accommodations, expenses: GRAIL, Merck, Menarini Silicon Biosystems, Pfizer, Genomic Health, AstraZeneca, Ionis Pharmaceuticals. Kathryn Ruddy. Patents, Royalties, Other Intellectual Property: My husband is a co-inventor of technology licensed by Mayo Clinic to AliveCor (MountainView, CA), which makes a smartphone-enabled remote ECG monitoring system. Richard Gelber. Research funding: AstraZeneca, Novartis, Roche, Merck, Pfizer. Travel, accommodations, expenses: Roche, AstraZeneca, Novartis. Bill Barry. Employment: Rho. Ann Partridge. Patents, Royalties, Other Intellectual Property: I receive small royalty payments for co-authoring the breast cancer survivorship section of UpToDate. Travel, accommodations, expenses: Novartis. Eric Winer. Honoraria: Genentech/Roche, Genomic Health. Consulting or advisory role: Leap Therapeutics, Seattle Genetics, Jounce Therapeutics, GlaxoSmithKline, Carrick Therapeutics, Lilly, G1 Therapeutics, Syros Pharmaceuticals, Genentech/Roche, Gilead Sciences, Zymeworks, Athenex. Research funding: Genentech. Other Relationship: InfiniteMD. Ian Krop. Employment: AMAG Pharmaceuticals, Freeline Therapeutics. Leadership: AMAG Pharmaceuticals, Freeline Therapeutics. Stock and other ownership interests: AMAG Pharmaceuticals, Freeline Therapeutics, Vertex. Honoraria: Genentech/Roche, AstraZeneca, Celltrion. Consulting or advisory role: Genentech/Roche, Seattle Genetics, Daiichi Sankyo, Macrogenics, Taiho Pharmaceutical, Context Therapeutics, Novartis, Merck, Ionis Pharmaceuticals, Bristol Myers Squibb, AstraZeneca. Research funding: Genentech, Pfizer. Sara Tolaney. Consulting or advisory role: Novartis, Pfizer, Merck, Lilly, Nektar, NanoString Technologies, AstraZeneca, Puma Biotechnology, Genentech, Eisai, Sanofi, Celldex, Bristol Myers Squibb, Paxman, Seattle Genetics, Odonate Therapeutics, AbbVie, Silverback Therapeutics, G1 Therapeutics, OncoPep, Kyowa Hakko Kirin, Samsung Bioepis, CytomX Therapeutics, Daiichi Sankyo, Athenex, Immunomedics/Gilead, Mersana, Certara. Research funding: Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, NanoString Technologies, Cyclacel, Nektar, Immunomedics, Odonate Therapeutics, Sanofi, Seattle Genetics. Travel, accommodations, expenses: AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Eisai, NanoString Technologies, Puma Biotechnology, Celldex. No other potential conflicts of interest were reported. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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
AB - 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
UR - http://www.scopus.com/inward/record.url?scp=85125263289&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85125263289&partnerID=8YFLogxK
U2 - 10.1038/s41523-022-00385-2
DO - 10.1038/s41523-022-00385-2
M3 - Article
AN - SCOPUS:85125263289
VL - 8
JO - npj Breast Cancer
JF - npj Breast Cancer
SN - 2374-4677
IS - 1
M1 - 18
ER -