TY - JOUR
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.
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/4
Y1 - 2020/4
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
UR - http://www.scopus.com/inward/record.url?scp=85072378847&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072378847&partnerID=8YFLogxK
U2 - 10.1016/j.clbc.2019.07.011
DO - 10.1016/j.clbc.2019.07.011
M3 - Article
C2 - 31558424
AN - SCOPUS:85072378847
SN - 1526-8209
VL - 20
SP - 145-151.e2
JO - Clinical breast cancer
JF - Clinical breast cancer
IS - 2
ER -