|Title||Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Freedman RA, Gelman RS, Agar NYR, Santagata S, Randall EC, Lopez BGimenez-Ca, Connolly RM, Dunn IF, Van Poznak CH, Anders CK, Melisko ME, Silvestri K, Cotter CM, Componeschi KP, Marte JM, Moy B, Blackwell KL, Puhalla SL, Ibrahim N, Moynihan TJ, Nangia J, Tung N, Burns R, Rimawi MF, Krop IE, Wolff AC, Winer EP, Lin NU|
|Corporate Authors||Translational Breast Cancer Research Consortium(TBCRC)|
|Journal||Clin Breast Cancer|
|Date Published||2020 Apr|
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.
|Alternate Journal||Clin. Breast Cancer|
|PubMed Central ID||PMC7035200|
|Grant List||R01 CA201469 / CA / NCI NIH HHS / United States |
P41 EB015898 / EB / NIBIB NIH HHS / United States
R25 CA089017 / CA / NCI NIH HHS / United States
P30 CA006516 / CA / NCI NIH HHS / United States
U54 CA210180 / CA / NCI NIH HHS / United States