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TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases

PURPOSE: Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from addition...

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Autores principales: Freedman, Rachel A., Gelman, Rebecca S., Anders, Carey K., Melisko, Michelle E., Parsons, Heather A., Cropp, Anne M., Silvestri, Kelly, Cotter, Christine M., Componeschi, Kathryn P., Marte, Juan M., Connolly, Roisin M., Moy, Beverly, Van Poznak, Catherine H., Blackwell, Kimberly L., Puhalla, Shannon L., Jankowitz, Rachel C., Smith, Karen L., Ibrahim, Nuhad, Moynihan, Timothy J., O’Sullivan, Ciara C., Nangia, Julie, Niravath, Polly, Tung, Nadine, Pohlmann, Paula R., Burns, Robyn, Rimawi, Mothaffar F., Krop, Ian E., Wolff, Antonio C., Winer, Eric P., Lin, Nancy U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Clinical Oncology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494354/
https://www.ncbi.nlm.nih.gov/pubmed/30860945
http://dx.doi.org/10.1200/JCO.18.01511
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author Freedman, Rachel A.
Gelman, Rebecca S.
Anders, Carey K.
Melisko, Michelle E.
Parsons, Heather A.
Cropp, Anne M.
Silvestri, Kelly
Cotter, Christine M.
Componeschi, Kathryn P.
Marte, Juan M.
Connolly, Roisin M.
Moy, Beverly
Van Poznak, Catherine H.
Blackwell, Kimberly L.
Puhalla, Shannon L.
Jankowitz, Rachel C.
Smith, Karen L.
Ibrahim, Nuhad
Moynihan, Timothy J.
O’Sullivan, Ciara C.
Nangia, Julie
Niravath, Polly
Tung, Nadine
Pohlmann, Paula R.
Burns, Robyn
Rimawi, Mothaffar F.
Krop, Ian E.
Wolff, Antonio C.
Winer, Eric P.
Lin, Nancy U.
author_facet Freedman, Rachel A.
Gelman, Rebecca S.
Anders, Carey K.
Melisko, Michelle E.
Parsons, Heather A.
Cropp, Anne M.
Silvestri, Kelly
Cotter, Christine M.
Componeschi, Kathryn P.
Marte, Juan M.
Connolly, Roisin M.
Moy, Beverly
Van Poznak, Catherine H.
Blackwell, Kimberly L.
Puhalla, Shannon L.
Jankowitz, Rachel C.
Smith, Karen L.
Ibrahim, Nuhad
Moynihan, Timothy J.
O’Sullivan, Ciara C.
Nangia, Julie
Niravath, Polly
Tung, Nadine
Pohlmann, Paula R.
Burns, Robyn
Rimawi, Mothaffar F.
Krop, Ian E.
Wolff, Antonio C.
Winer, Eric P.
Lin, Nancy U.
author_sort Freedman, Rachel A.
collection PubMed
description PURPOSE: Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from additional study cohorts. PATIENTS AND METHODS: Patients with measurable, progressive, HER2-positive brain metastases (92% after receiving CNS surgery and/or radiotherapy) received neratinib 240 mg orally once per day plus capecitabine 750 mg/m(2) twice per day for 14 days, then 7 days off. Lapatinib-naïve (cohort 3A) and lapatinib-treated (cohort 3B) patients were enrolled. If nine or more of 35 (cohort 3A) or three or more of 25 (cohort 3B) had CNS objective response rates (ORR), the drug combination would be deemed promising. The primary end point was composite CNS ORR in each cohort separately, requiring a reduction of 50% or more in the sum of target CNS lesion volumes without progression of nontarget lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression. RESULTS: Forty-nine patients enrolled in cohorts 3A (n = 37) and 3B (n = 12; cohort closed for slow accrual). In cohort 3A, the composite CNS ORR = 49% (95% CI, 32% to 66%), and the CNS ORR in cohort 3B = 33% (95% CI, 10% to 65%). Median progression-free survival was 5.5 and 3.1 months in cohorts 3A and 3B, respectively; median survival was 13.3 and 15.1 months. Diarrhea was the most common grade 3 toxicity (29% in cohorts 3A and 3B). CONCLUSION: Neratinib plus capecitabine is active against refractory, HER2-positive breast cancer brain metastases, adding additional evidence that the efficacy of HER2-directed therapy in the brain is enhanced by chemotherapy. For optimal tolerance, efforts to minimize diarrhea are warranted.
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spelling pubmed-64943542019-11-20 TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases Freedman, Rachel A. Gelman, Rebecca S. Anders, Carey K. Melisko, Michelle E. Parsons, Heather A. Cropp, Anne M. Silvestri, Kelly Cotter, Christine M. Componeschi, Kathryn P. Marte, Juan M. Connolly, Roisin M. Moy, Beverly Van Poznak, Catherine H. Blackwell, Kimberly L. Puhalla, Shannon L. Jankowitz, Rachel C. Smith, Karen L. Ibrahim, Nuhad Moynihan, Timothy J. O’Sullivan, Ciara C. Nangia, Julie Niravath, Polly Tung, Nadine Pohlmann, Paula R. Burns, Robyn Rimawi, Mothaffar F. Krop, Ian E. Wolff, Antonio C. Winer, Eric P. Lin, Nancy U. J Clin Oncol ORIGINAL REPORTS PURPOSE: Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from additional study cohorts. PATIENTS AND METHODS: Patients with measurable, progressive, HER2-positive brain metastases (92% after receiving CNS surgery and/or radiotherapy) received neratinib 240 mg orally once per day plus capecitabine 750 mg/m(2) twice per day for 14 days, then 7 days off. Lapatinib-naïve (cohort 3A) and lapatinib-treated (cohort 3B) patients were enrolled. If nine or more of 35 (cohort 3A) or three or more of 25 (cohort 3B) had CNS objective response rates (ORR), the drug combination would be deemed promising. The primary end point was composite CNS ORR in each cohort separately, requiring a reduction of 50% or more in the sum of target CNS lesion volumes without progression of nontarget lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression. RESULTS: Forty-nine patients enrolled in cohorts 3A (n = 37) and 3B (n = 12; cohort closed for slow accrual). In cohort 3A, the composite CNS ORR = 49% (95% CI, 32% to 66%), and the CNS ORR in cohort 3B = 33% (95% CI, 10% to 65%). Median progression-free survival was 5.5 and 3.1 months in cohorts 3A and 3B, respectively; median survival was 13.3 and 15.1 months. Diarrhea was the most common grade 3 toxicity (29% in cohorts 3A and 3B). CONCLUSION: Neratinib plus capecitabine is active against refractory, HER2-positive breast cancer brain metastases, adding additional evidence that the efficacy of HER2-directed therapy in the brain is enhanced by chemotherapy. For optimal tolerance, efforts to minimize diarrhea are warranted. American Society of Clinical Oncology 2019-05-01 2019-03-12 /pmc/articles/PMC6494354/ /pubmed/30860945 http://dx.doi.org/10.1200/JCO.18.01511 Text en © 2019 by American Society of Clinical Oncology https://creativecommons.org/licenses/by/4.0/ Licensed under the Creative Commons Attribution 4.0 License: https://creativecommons.org/licenses/by/4.0/
spellingShingle ORIGINAL REPORTS
Freedman, Rachel A.
Gelman, Rebecca S.
Anders, Carey K.
Melisko, Michelle E.
Parsons, Heather A.
Cropp, Anne M.
Silvestri, Kelly
Cotter, Christine M.
Componeschi, Kathryn P.
Marte, Juan M.
Connolly, Roisin M.
Moy, Beverly
Van Poznak, Catherine H.
Blackwell, Kimberly L.
Puhalla, Shannon L.
Jankowitz, Rachel C.
Smith, Karen L.
Ibrahim, Nuhad
Moynihan, Timothy J.
O’Sullivan, Ciara C.
Nangia, Julie
Niravath, Polly
Tung, Nadine
Pohlmann, Paula R.
Burns, Robyn
Rimawi, Mothaffar F.
Krop, Ian E.
Wolff, Antonio C.
Winer, Eric P.
Lin, Nancy U.
TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
title TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
title_full TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
title_fullStr TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
title_full_unstemmed TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
title_short TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
title_sort tbcrc 022: a phase ii trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2–positive breast cancer and brain metastases
topic ORIGINAL REPORTS
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494354/
https://www.ncbi.nlm.nih.gov/pubmed/30860945
http://dx.doi.org/10.1200/JCO.18.01511
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