Trastuzumab emtansine for HER2-positive advanced breast cancer
Open accessAbstract
BACKGROUND: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1. The antibody and the cytotoxic agent are conjugated by means of a stable linker. METHODS: We randomly assigned patients with HER2-positive advanced breast cancer, who had previously been treated with trastuzumab and a taxane, to T-DM1 or lapatinib plus capecitabine. The primary end points were progression-free survival (as assessed by independent review), overall survival, and safety. Secondary end points included progression-free survival (investigator-assessed), the objective response rate, and the time to symptom progression. Two interim analyses of overall survival were conducted. RESULTS: Among 991 randomly assigned patients, median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine (hazard ratio for progression or death from any cause, 0.65; 95% confidence interval [CI], 0.55 to 0.77; P<0.001), and median overall survival at the second interim analysis crossed the stopping boundary for efficacy (30.9 months vs. 25.1 months; hazard ratio for death from any cause, 0.68; 95% CI, 0.55 to 0.85; P<0.001). The objective response rate was higher with T-DM1 (43.6%, vs. 30.8% with lapatinib plus capecitabine; P<0.001); results for all additional secondary end points favored T-DM1. Rates of grade 3 or 4 adverse events were higher with lapatinib plus capecitabine than with T-DM1 (57% vs. 41%). The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1, whereas the incidences of diarrhea, nausea, vomiting, and palmar-plantar erythrodysesthesia were higher with lapatinib plus capecitabine. CONCLUSIONS: T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane. (Funded by F. Hoffmann-La Roche/Genentech; EMILIA ClinicalTrials.gov number, NCT00829166.).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the field testing, T-DM1 compared with lapatinib plus capecitabine in second-line metastatic breast cancer after trastuzumab failure was assigned ESMO-MCBS grade 5.
“T-DM1 versus lapatinib + | EMILIA | Second-line metastatic after | PFS and OS | 6.4 months | 3.2 months 0.65 (0.55-0.77) 25 months | 6.8 months 0.68 (0.55-0.85) Delayed deterioration | 5 | [57, 58]”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660 · see citing works
Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A., & McGuire, W. L. (1987) · Science · doi:10.1126/science.3798106 · Cited by 11,760 · see citing works
Slamon, D. J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Eiermann, W., Wolter, J., Pegram, M., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103153441101 · Cited by 11,500 · see citing works
Self-citationLapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer
Geyer, C. E., Forster, J. K., Lindquist, D. L., Chan, S. Y. T., Romieu, C. G., Pieńkowski, T., Jagiełło-Gruszfeld, A., Crown, J. P., Chan, A., Kaufman, B., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa064320 · Cited by 3,426 · see citing works
Brady, M. J., Cella, D. F., Mo, F., Bonomi, A. E., Tulsky, D. S., Lloyd, S. R., Deasy, S., Cobleigh, M., & Shiomoto, G. (1997) · Journal of Clinical Oncology · doi:10.1200/jco.1997.15.3.974 · Cited by 1,752 · see citing works
Targeting HER2-Positive Breast Cancer with Trastuzumab-DM1, an Antibody–Cytotoxic Drug Conjugate
Phillips, G. D. L., Li, G., Dugger, D. L., Crocker, L., Parsons, K. L., Mai, E., Blättler, W. A., Lambert, J. M., Chari, R. V. J., Lutz, R. J., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1776 · Cited by 1,679 · see citing works
Marty, M. E., Cognetti, F., Maraninchi, D., Snyder, R., Mauriac, L., Tubiana-Hulin, M., Chan, S. Y. T., Grimes, D., Antón, A., Lluch, A. M., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.173 · Cited by 1,588 · see citing works
Lamon, D. E. J. S., Eyland, B. R. L., Hak, S. T. S., Uchs, H. A. F., Aton, V. I. P., Ajamonde, A. L. B., LeMing, T., Iermann, W. O. E., Olter, J. A. W., Egram, M. A. P., et al. (2009) · Cited by 1,199 · see citing works
Ross, J. S., Slodkowska, E. A., Symmans, W. F., Pusztai, L., Ravdin, P. M., & Hortobágyi, G. N. (2009) · The Oncologist · doi:10.1634/theoncologist.2008-0230 · Cited by 1,144 · see citing works
Burris, H. A., Rugo, H. S., Vukelja, S. J., Vogel, C. L., Borson, R. A., Limentani, S. A., Tan-Chiu, E., Krop, I. E., Michaelson, R. A., Girish, S., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.29.5865 · Cited by 763 · see citing works
Self-citationDawood, S. S., Broglio, K. R., Buzdar, A. U., Hortobágyi, G. N., & Giordano, S. H. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.19.9844 · Cited by 759 · see citing works
Junttila, T. T., Li, G., Parsons, K. L., Phillips, G. D. L., & Sliwkowski, M. X. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-010-1090-x · Cited by 542 · see citing works
Krop, I. E., LoRusso, P. M., Miller, K. D., Modi, S., Yardley, D. A., Rodriguez, G., Guardino, E., Lu, M. W., Zheng, M., Girish, S., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.40.5902 · Cited by 366 · see citing works
Self-citationHurvitz, S. A., Dirix, L. Y., Kocsis, J., et al. (2011) · European Journal of Cancer · doi:10.1016/s0959-8049(11)71443-5 · Cited by 54 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Trastuzumab deruxtecan in previously treated HER2-positive breast cancer
Modi, S., Saura, C., Yamashita, T., Park, Y. H., Kim, S.-B., Tamura, K., Andre, F., Iwata, H., Ito, Y., Tsurutani, J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1914510 · Cited by 2,006 · see citing works
Self-citationThe evolution of commercial drug delivery technologies
Vargason, A. M., Anselmo, A. C., & Mitragotri, S. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00698-w · Cited by 1,361 · see citing works
Anselmo, A. C., & Mitragotri, S. (2016) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10003 · Cited by 1,321 · see citing works
ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics
Arteaga, C. L., & Engelman, J. A. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.025 · Cited by 1,048 · see citing works
Swain, S. M., Kim, S.-B., Cortés, J., Ro, J., Semiglazov, V., Campone, M., Ciruelos, E., Ferrero, J.-M., Schneeweiss, A., Knott, A., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70130-x · Cited by 1,006 · see citing works
Self-citationAntibody–Drug Conjugates: An Emerging Concept in Cancer Therapy
Chari, R. V. J., Miller, M. L., & Widdison, W. C. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201307628 · Cited by 930 · see citing works
Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer
Bardia, A., Mayer, I. A., Vahdat, L. T., Tolaney, S. M., Isakoff, S. J., Diamond, J. R., O’Shaughnessy, J., Moroose, R. L., Santin, A. D., Abramson, V. G., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1814213 · Cited by 874 · see citing works
Cherny, N. I., Sullivan, R., Dafni, U., Kerst, J. M., Sobrero, A., Zielinski, C., de Vries, E. G. E., & Piccart, M. J. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv249 · Cited by 818 · see citing works
Ogitani, Y., Hagihara, K., Oitate, M., Naito, H., & Agatsuma, T. (2016) · Cancer Science · doi:10.1111/cas.12966 · Cited by 751 · see citing works
ESMO-magnitude of clinical benefit scale version 1.1
Cherny, N. I., Dafni, U., Bogaerts, J., Latino, N. J., Pentheroudakis, G., Douillard, J.-Y., Tabernero, J., Zielinski, C., Piccart, M. J., & de Vries, E. G. E. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx310 · Cited by 641 · see citing works
Saura, C., Oliveira, M., Feng, Y.-H., Dai, M.-S., Chen, S.-W., Hurvitz, S. A., Kim, S.-B., Moy, B., Delaloge, S., Gradishar, W., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.20.00147 · Cited by 604 · see citing works
Antibody–drug conjugates for cancer therapy
Thomas, A., Teicher, B. A., & Hassan, R. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30030-4 · Cited by 606 · see citing works
ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2)
Cardoso, F., Costa, A., Norton, L., Senkus, E., Aapro, M., André, F., Barrios, C. H., Bergh, J., Biganzoli, L., Blackwell, K. L., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu385 · Cited by 540 · see citing works
“lapatinib plus capecitabine in the subset of 118 patients who were randomized in the first-line setting, having relapsed on or within 6 months of adjuvant trastuzumab, appeared similar to the effect seen in the overall trial [100].”
BackgroundResultSelf-citationMechanisms of ADC Toxicity and Strategies to Increase ADC Tolerability
Nguyen, T. D., Bordeau, B. M., & Balthasar, J. P. (2023) · Cancers · doi:10.3390/cancers15030713 · Cited by 441 · see citing works
Glucose Conjugation for the Specific Targeting and Treatment of Cancer
Calvaresi, E. C., & Hergenrother, P. J. (2013) · Chemical Science · doi:10.1039/c3sc22205e · Cited by 398 · see citing works
ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2)
Cardoso, F., Costa, A., Norton, L., Senkus, E., Aapro, M., André, F., Barrios, C. H., Bergh, J., Biganzoli, L., Blackwell, K. L., et al. (2014) · The Breast · doi:10.1016/j.breast.2014.08.009 · Cited by 338 · see citing works
Self-citationAntibody–Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review
Lambert, J. M., & Morris, C. Q. (2017) · Advances in Therapy · doi:10.1007/s12325-017-0519-6 · Cited by 304 · see citing works
Optimizing the safety of antibody–drug conjugates for patients with solid tumours
Tarantino, P., Ricciuti, B., Pradhan, S. M., & Tolaney, S. M. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00783-w · Cited by 269 · see citing works
Pivot, X., Manikhas, A., Żurawski, B., Chmielowska, E., Karaszewska, B., Allerton, R., Chan, S., Fabi, A., Bidoli, P., Gori, S., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.57.1794 · Cited by 242 · see citing works
The Journey of Antibody–Drug Conjugates: Lessons Learned from 40 Years of Development
Colombo, R., Tarantino, P., Rich, J. R., LoRusso, P. M., & de Vries, E. G. E. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0708 · Cited by 254 · see citing works
Robichaux, J. P., Elamin, Y. Y., Vijayan, R. S. K., Nilsson, M. B., Hu, L., He, J., Zhang, F., Pisegna, M., Poteete, A., Sun, H., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.09.001 · Cited by 242 · see citing works
Co-delivery of chemotherapeutics and proteins for synergistic therapy
He, C., Tang, Z., Tian, H., & Chen, X. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.10.021 · Cited by 231 · see citing works
A review of the clinical efficacy of FDA-approved antibody‒drug conjugates in human cancers
Liu, K., Li, M., Li, Y., Li, Y., Chen, Z., Tang, Y., Yang, M., Deng, G., & Liu, H. (2024) · Molecular Cancer · doi:10.1186/s12943-024-01963-7 · Cited by 196 · see citing works
Zhu, Y., Liu, K., Wang, K., & Zhu, H. (2023) · Cancer · doi:10.1002/cncr.34507 · Cited by 192 · see citing works
The solute carrier SLC35F2 enables YM155-mediated DNA damage toxicity
Winter, G. E., Radic, B., Mayor-Ruiz, C., Blomen, V. A., Trefzer, C., Kandasamy, R. K., Huber, K. V. M., Gridling, M., Chen, D., Klampfl, T., et al. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1590 · Cited by 175 · see citing works
Ioannidis, J. P. A., Kim, B. Y. S., & Trounson, A. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0314-y · Cited by 175 · see citing works
Targeted therapy for breast cancer and molecular mechanisms of resistance to treatment
Gu, G., Dustin, D., & Fuqua, S. A. (2016) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2016.11.005 · Cited by 163 · see citing works
Jhaveri, K. L., Wang, X. V., Makker, V., Luoh, S.-W., Mitchell, E. P., Zwiebel, J. A., Sharon, E., Gray, R. J., Li, S., McShane, L. M., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz291 · Cited by 151 · see citing works
Curative Properties of Noninternalizing Antibody–Drug Conjugates Based on Maytansinoids
Perrino, E., Steiner, M., Krall, N., Bernardes, G. J. L., Pretto, F., Casi, G., & Neri, D. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2990 · Cited by 130 · see citing works
Raghav, K., Loree, J. M., Morris, J. S., Overman, M. J., Yu, R., Meric-Bernstam, F., Menter, D., Korphaisarn, K., Kee, B., Muranyi, A., et al. (2019) · JCO Precision Oncology · doi:10.1200/po.18.00226 · Cited by 132 · see citing works
Welslau, M., Diéras, V., Sohn, J., Hurvitz, S. A., Lalla, D., Fang, L., Althaus, B., Guardino, E., & Miles, D. (2014) · Cancer · doi:10.1002/cncr.28465 · Cited by 126 · see citing works
U3-1402, a Novel HER3-Targeting Antibody-Drug Conjugate, for the Treatment of Colorectal Cancer
Koganemaru, S., Kuboki, Y., Koga, Y., Kojima, T., Yamauchi, M., Maeda, N., Kagari, T., Hirotani, K., Yasunaga, M., Matsumura, Y., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-0452 · Cited by 90 · see citing works
Kashyap, A. S., Fernandez-Rodriguez, L., Zhao, Y., Monaco, G., Trefny, M. P., Yoshida, N., Martin, K., Sharma, A., Olieric, N., Shah, P., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.057 · Cited by 76 · see citing works
Wallwiener, M., Matthies, L., Simoes, E., Keilmann, L., Hartkopf, A. D., Sokolov, A. N., Walter, C. B., Sickenberger, N., Wallwiener, S., Feisst, M., et al. (2017) · Journal of Medical Internet Research · doi:10.2196/jmir.8210 · Cited by 55 · see citing works
The significance of the trial outcome was associated with publication rate and time to publication
Song, S. Y., Koo, D.-H., Jung, S.-Y., Kang, W., & Kim, E. Y. (2017) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2017.02.009 · Cited by 36 · see citing works
Ultrasmall silica nanoparticles in translational biomedical research: Overview and outlook
Singh, N., Shi, S., & Goel, S. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114638 · Cited by 35 · see citing works
McHugh, D., Eisenberger, M., Heath, E. I., Bruce, J., Danila, D. C., Rathkopf, D. E., Feldman, J., Slovin, S. F., Anand, B., Chu, R., et al. (2019) · Investigational New Drugs · doi:10.1007/s10637-019-00731-5 · Cited by 23 · see citing works
- Authors
- Verma, S., Miles, D., Gianni, L., Krop, I. E., Welslau, M., Baselga, J., Pegram, M., Oh, D.-Y., Diéras, V., Guardino, E., Fang, L., Lu, M. W., Olsen, S., & Blackwell, K.
- Affiliations
- Sunnybrook Health Science Centre (CA)
- Mount Vernon Hospital (GB)
- IRCCS Ospedale San Raffaele (IT)
- Dana-Farber Cancer Institute (US)
- Klinikum Aschaffenburg (DE)
- University of Miami (US)
- Seoul National University (KR)
- Genentech (US)
- Duke Medical Center (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2012-11-08
- Volume
- 367
- Issue
- 19
- Pages
- 1783-1791
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC5125250
- OpenAlex
- W2159967578
- Cited by
- 3,834
- References
- 14
- Citations by year
- 2026: 207 · 2025: 263 · 2024: 265 · 2023: 286 · 2022: 317 · 2021: 311 · 2020: 287 · 2019: 279 · 2018: 252 · 2017: 282 · 2016: 285 · 2015: 282 · 2014: 291 · 2013: 206 · 2012: 17
- FWCI
- 125.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Keywords
- trastuzumab emtansine, HER2-positive breast cancer, advanced breast cancer, antibody-drug conjugates, lapatinib, capecitabine, progression-free survival, overall survival, objective response rate, adverse events, thrombocytopenia, drug toxicity, trastuzumab, taxane pretreatment, HER2-targeted therapy
- MeSH terms
- Trastuzumab, Capecitabine, Lapatinib, Ado-Trastuzumab Emtansine, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Deoxycytidine, Female, Fluorouracil, Humans, Maytansine, Middle Aged, Neoplasm Metastasis, Quinazolines, Survival Rate, Disease-Free Survival, Erb-b2 Receptor Tyrosine Kinases, Kaplan-Meier Estimate, Young Adult, Intention to Treat Analysis, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
