Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022

Translational Breast Cancer Research Consortium (TBCRC)

Research output: Contribution to journalArticle

Abstract

Purpose: This pilot study was performed to test our ability to administer neratinib monotherapy before clinically recommended craniotomy in patients with HER2-positive metastatic breast cancer to the central nervous system, to examine neratinib's central nervous system penetration at craniotomy, and to examine postoperative neratinib maintenance. Patients and Methods: Patients with HER2-positive brain metastases undergoing clinically indicated cranial resection of a parenchymal tumor received neratinib 240 mg orally once a day for 7 to 21 days preoperatively, and resumed therapy postoperatively in 28-day cycles. Exploratory evaluations of time to disease progression, survival, and correlative tissue, cerebrospinal fluid (CSF), and blood-based analyses examining neratinib concentrations were planned. The study was registered at ClinicalTrials.gov under number NCT01494662. Results: We enrolled 5 patients between May 22, 2013, and October 18, 2016. As of March 1, 2019, patients had remained on the study protocol for 1 to 75+ postoperative cycles pf therapy. Two patients had grade 3 diarrhea. Evaluation of the CSF showed low concentrations of neratinib; nonetheless, 2 patients continued to receive therapy without disease progression for at least 13 cycles, with one on-study treatment lasting for nearly 6 years. Neratinib distribution in surgical tissue was variable for 1 patient, while specimens from 2 others did not produce conclusive results as a result of limited available samples. Conclusion: Neratinib resulted in expected rates of diarrhea in this small cohort, with 2 of 5 patients receiving the study treatment for durable periods. Although logistically challenging, we were able to test a limited number of CSF- and parenchymal-based neratinib concentrations. Our findings from resected tumor tissue in one patient revealed heterogeneity in drug distribution and tumor histopathology.

Original languageEnglish (US)
JournalClinical Breast Cancer
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Brain Neoplasms
Breast Neoplasms
Neoplasm Metastasis
Research
Cerebrospinal Fluid
Craniotomy
Disease Progression
Diarrhea
Central Nervous System
N-(4-(3-chloro-4-(2-pyridinylmethoxy)anilino)-3-cyano-7-ethoxy-6-quinolyl)-4-(dimethylamino)-2-butenamide
Therapeutics
Tissue Survival
Neoplasms
Maintenance
Brain

Keywords

  • Central nervous system
  • Metastatic

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases : Translational Breast Cancer Research Consortium 022. / Translational Breast Cancer Research Consortium (TBCRC).

In: Clinical Breast Cancer, 01.01.2019.

Research output: Contribution to journalArticle

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title = "Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022",
abstract = "Purpose: This pilot study was performed to test our ability to administer neratinib monotherapy before clinically recommended craniotomy in patients with HER2-positive metastatic breast cancer to the central nervous system, to examine neratinib's central nervous system penetration at craniotomy, and to examine postoperative neratinib maintenance. Patients and Methods: Patients with HER2-positive brain metastases undergoing clinically indicated cranial resection of a parenchymal tumor received neratinib 240 mg orally once a day for 7 to 21 days preoperatively, and resumed therapy postoperatively in 28-day cycles. Exploratory evaluations of time to disease progression, survival, and correlative tissue, cerebrospinal fluid (CSF), and blood-based analyses examining neratinib concentrations were planned. The study was registered at ClinicalTrials.gov under number NCT01494662. Results: We enrolled 5 patients between May 22, 2013, and October 18, 2016. As of March 1, 2019, patients had remained on the study protocol for 1 to 75+ postoperative cycles pf therapy. Two patients had grade 3 diarrhea. Evaluation of the CSF showed low concentrations of neratinib; nonetheless, 2 patients continued to receive therapy without disease progression for at least 13 cycles, with one on-study treatment lasting for nearly 6 years. Neratinib distribution in surgical tissue was variable for 1 patient, while specimens from 2 others did not produce conclusive results as a result of limited available samples. Conclusion: Neratinib resulted in expected rates of diarrhea in this small cohort, with 2 of 5 patients receiving the study treatment for durable periods. Although logistically challenging, we were able to test a limited number of CSF- and parenchymal-based neratinib concentrations. Our findings from resected tumor tissue in one patient revealed heterogeneity in drug distribution and tumor histopathology.",
keywords = "Central nervous system, Metastatic",
author = "{Translational Breast Cancer Research Consortium (TBCRC)} and Freedman, {Rachel A.} and Gelman, {Rebecca S.} and Agar, {Nathalie Y.R.} and Sandro Santagata and Randall, {Elizabeth C.} and {Gimenez-Cassina Lopez}, Bego{\~n}a and Connolly, {Roisin M.} and Dunn, {Ian F.} and {Van Poznak}, {Catherine H.} and Anders, {Carey K.} and Melisko, {Michelle E.} and Kelly Silvestri and Cotter, {Christine M.} and Componeschi, {Kathryn P.} and Marte, {Juan M.} and Beverly Moy and Blackwell, {Kimberly L.} and Puhalla, {Shannon L.} and Nuhad Ibrahim and Moynihan, {Timothy J.} and Julie Nangia and Nadine Tung and Robyn Burns and Rimawi, {Mothaffar F.} and Krop, {Ian E.} and Wolff, {Antonio C.} and Winer, {Eric P.} and Lin, {Nancy U.}",
year = "2019",
month = "1",
day = "1",
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language = "English (US)",
journal = "Clinical Breast Cancer",
issn = "1526-8209",
publisher = "Elsevier",

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T1 - Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases

T2 - Translational Breast Cancer Research Consortium 022

AU - Translational Breast Cancer Research Consortium (TBCRC)

AU - Freedman, Rachel A.

AU - Gelman, Rebecca S.

AU - Agar, Nathalie Y.R.

AU - Santagata, Sandro

AU - Randall, Elizabeth C.

AU - Gimenez-Cassina Lopez, Begoña

AU - Connolly, Roisin M.

AU - Dunn, Ian F.

AU - Van Poznak, Catherine H.

AU - Anders, Carey K.

AU - Melisko, Michelle E.

AU - Silvestri, Kelly

AU - Cotter, Christine M.

AU - Componeschi, Kathryn P.

AU - Marte, Juan M.

AU - Moy, Beverly

AU - Blackwell, Kimberly L.

AU - Puhalla, Shannon L.

AU - Ibrahim, Nuhad

AU - Moynihan, Timothy J.

AU - Nangia, Julie

AU - Tung, Nadine

AU - Burns, Robyn

AU - Rimawi, Mothaffar F.

AU - Krop, Ian E.

AU - Wolff, Antonio C.

AU - Winer, Eric P.

AU - Lin, Nancy U.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: This pilot study was performed to test our ability to administer neratinib monotherapy before clinically recommended craniotomy in patients with HER2-positive metastatic breast cancer to the central nervous system, to examine neratinib's central nervous system penetration at craniotomy, and to examine postoperative neratinib maintenance. Patients and Methods: Patients with HER2-positive brain metastases undergoing clinically indicated cranial resection of a parenchymal tumor received neratinib 240 mg orally once a day for 7 to 21 days preoperatively, and resumed therapy postoperatively in 28-day cycles. Exploratory evaluations of time to disease progression, survival, and correlative tissue, cerebrospinal fluid (CSF), and blood-based analyses examining neratinib concentrations were planned. The study was registered at ClinicalTrials.gov under number NCT01494662. Results: We enrolled 5 patients between May 22, 2013, and October 18, 2016. As of March 1, 2019, patients had remained on the study protocol for 1 to 75+ postoperative cycles pf therapy. Two patients had grade 3 diarrhea. Evaluation of the CSF showed low concentrations of neratinib; nonetheless, 2 patients continued to receive therapy without disease progression for at least 13 cycles, with one on-study treatment lasting for nearly 6 years. Neratinib distribution in surgical tissue was variable for 1 patient, while specimens from 2 others did not produce conclusive results as a result of limited available samples. Conclusion: Neratinib resulted in expected rates of diarrhea in this small cohort, with 2 of 5 patients receiving the study treatment for durable periods. Although logistically challenging, we were able to test a limited number of CSF- and parenchymal-based neratinib concentrations. Our findings from resected tumor tissue in one patient revealed heterogeneity in drug distribution and tumor histopathology.

AB - Purpose: This pilot study was performed to test our ability to administer neratinib monotherapy before clinically recommended craniotomy in patients with HER2-positive metastatic breast cancer to the central nervous system, to examine neratinib's central nervous system penetration at craniotomy, and to examine postoperative neratinib maintenance. Patients and Methods: Patients with HER2-positive brain metastases undergoing clinically indicated cranial resection of a parenchymal tumor received neratinib 240 mg orally once a day for 7 to 21 days preoperatively, and resumed therapy postoperatively in 28-day cycles. Exploratory evaluations of time to disease progression, survival, and correlative tissue, cerebrospinal fluid (CSF), and blood-based analyses examining neratinib concentrations were planned. The study was registered at ClinicalTrials.gov under number NCT01494662. Results: We enrolled 5 patients between May 22, 2013, and October 18, 2016. As of March 1, 2019, patients had remained on the study protocol for 1 to 75+ postoperative cycles pf therapy. Two patients had grade 3 diarrhea. Evaluation of the CSF showed low concentrations of neratinib; nonetheless, 2 patients continued to receive therapy without disease progression for at least 13 cycles, with one on-study treatment lasting for nearly 6 years. Neratinib distribution in surgical tissue was variable for 1 patient, while specimens from 2 others did not produce conclusive results as a result of limited available samples. Conclusion: Neratinib resulted in expected rates of diarrhea in this small cohort, with 2 of 5 patients receiving the study treatment for durable periods. Although logistically challenging, we were able to test a limited number of CSF- and parenchymal-based neratinib concentrations. Our findings from resected tumor tissue in one patient revealed heterogeneity in drug distribution and tumor histopathology.

KW - Central nervous system

KW - Metastatic

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U2 - 10.1016/j.clbc.2019.07.011

DO - 10.1016/j.clbc.2019.07.011

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JO - Clinical Breast Cancer

JF - Clinical Breast Cancer

SN - 1526-8209

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