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Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

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Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. / Murthy, Rashmi K; Loi, Sherene; Okines, Alicia; Paplomata, Elisavet; Hamilton, Erika; Hurvitz, Sara A; Lin, Nancy U; Borges, Virginia; Abramson, Vandana; Anders, Carey; Bedard, Philippe L; Oliveira, Mafalda; Jakobsen, Erik; Bachelot, Thomas; Shachar, Shlomit S; Müller, Volkmar; Braga, Sofia; Duhoux, Francois P; Greil, Richard; Cameron, David; Carey, Lisa A; Curigliano, Giuseppe; Gelmon, Karen; Hortobagyi, Gabriel; Krop, Ian; Loibl, Sibylle; Pegram, Mark; Slamon, Dennis; Palanca-Wessels, M Corinna; Walker, Luke; Feng, Wentao; Winer, Eric P.

in: NEW ENGL J MED, Jahrgang 382, Nr. 7, 13.02.2020, S. 597-609.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Murthy, RK, Loi, S, Okines, A, Paplomata, E, Hamilton, E, Hurvitz, SA, Lin, NU, Borges, V, Abramson, V, Anders, C, Bedard, PL, Oliveira, M, Jakobsen, E, Bachelot, T, Shachar, SS, Müller, V, Braga, S, Duhoux, FP, Greil, R, Cameron, D, Carey, LA, Curigliano, G, Gelmon, K, Hortobagyi, G, Krop, I, Loibl, S, Pegram, M, Slamon, D, Palanca-Wessels, MC, Walker, L, Feng, W & Winer, EP 2020, 'Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer', NEW ENGL J MED, Jg. 382, Nr. 7, S. 597-609. https://doi.org/10.1056/NEJMoa1914609

APA

Murthy, R. K., Loi, S., Okines, A., Paplomata, E., Hamilton, E., Hurvitz, S. A., Lin, N. U., Borges, V., Abramson, V., Anders, C., Bedard, P. L., Oliveira, M., Jakobsen, E., Bachelot, T., Shachar, S. S., Müller, V., Braga, S., Duhoux, F. P., Greil, R., ... Winer, E. P. (2020). Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. NEW ENGL J MED, 382(7), 597-609. https://doi.org/10.1056/NEJMoa1914609

Vancouver

Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. NEW ENGL J MED. 2020 Feb 13;382(7):597-609. https://doi.org/10.1056/NEJMoa1914609

Bibtex

@article{110bec3a2cd64c9fa18af6f2dd629100,
title = "Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer",
abstract = "BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase.METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety.RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group.CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.).",
keywords = "Aged, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Brain Neoplasms/secondary, Breast Neoplasms/drug therapy, Capecitabine/administration & dosage, Consolidation Chemotherapy, Diarrhea/chemically induced, Double-Blind Method, Female, Humans, Kaplan-Meier Estimate, Middle Aged, Oxazoles/administration & dosage, Progression-Free Survival, Protein-Tyrosine Kinases/antagonists & inhibitors, Pyridines/administration & dosage, Quinazolines/administration & dosage, Receptor, ErbB-2/analysis, Trastuzumab/administration & dosage",
author = "Murthy, {Rashmi K} and Sherene Loi and Alicia Okines and Elisavet Paplomata and Erika Hamilton and Hurvitz, {Sara A} and Lin, {Nancy U} and Virginia Borges and Vandana Abramson and Carey Anders and Bedard, {Philippe L} and Mafalda Oliveira and Erik Jakobsen and Thomas Bachelot and Shachar, {Shlomit S} and Volkmar M{\"u}ller and Sofia Braga and Duhoux, {Francois P} and Richard Greil and David Cameron and Carey, {Lisa A} and Giuseppe Curigliano and Karen Gelmon and Gabriel Hortobagyi and Ian Krop and Sibylle Loibl and Mark Pegram and Dennis Slamon and Palanca-Wessels, {M Corinna} and Luke Walker and Wentao Feng and Winer, {Eric P}",
note = "Copyright {\textcopyright} 2019 Massachusetts Medical Society.",
year = "2020",
month = feb,
day = "13",
doi = "10.1056/NEJMoa1914609",
language = "English",
volume = "382",
pages = "597--609",
journal = "NEW ENGL J MED",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "7",

}

RIS

TY - JOUR

T1 - Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

AU - Murthy, Rashmi K

AU - Loi, Sherene

AU - Okines, Alicia

AU - Paplomata, Elisavet

AU - Hamilton, Erika

AU - Hurvitz, Sara A

AU - Lin, Nancy U

AU - Borges, Virginia

AU - Abramson, Vandana

AU - Anders, Carey

AU - Bedard, Philippe L

AU - Oliveira, Mafalda

AU - Jakobsen, Erik

AU - Bachelot, Thomas

AU - Shachar, Shlomit S

AU - Müller, Volkmar

AU - Braga, Sofia

AU - Duhoux, Francois P

AU - Greil, Richard

AU - Cameron, David

AU - Carey, Lisa A

AU - Curigliano, Giuseppe

AU - Gelmon, Karen

AU - Hortobagyi, Gabriel

AU - Krop, Ian

AU - Loibl, Sibylle

AU - Pegram, Mark

AU - Slamon, Dennis

AU - Palanca-Wessels, M Corinna

AU - Walker, Luke

AU - Feng, Wentao

AU - Winer, Eric P

N1 - Copyright © 2019 Massachusetts Medical Society.

PY - 2020/2/13

Y1 - 2020/2/13

N2 - BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase.METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety.RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group.CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.).

AB - BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase.METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety.RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group.CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.).

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Brain Neoplasms/secondary

KW - Breast Neoplasms/drug therapy

KW - Capecitabine/administration & dosage

KW - Consolidation Chemotherapy

KW - Diarrhea/chemically induced

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Kaplan-Meier Estimate

KW - Middle Aged

KW - Oxazoles/administration & dosage

KW - Progression-Free Survival

KW - Protein-Tyrosine Kinases/antagonists & inhibitors

KW - Pyridines/administration & dosage

KW - Quinazolines/administration & dosage

KW - Receptor, ErbB-2/analysis

KW - Trastuzumab/administration & dosage

U2 - 10.1056/NEJMoa1914609

DO - 10.1056/NEJMoa1914609

M3 - SCORING: Journal article

C2 - 31825569

VL - 382

SP - 597

EP - 609

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 7

ER -