Neratinib: the emergence of a new player in the management of HER2+ breast cancer brain metastasis

Nasrazadani, Azadeh; Brufsky, Adam

doi:10.2217/fon-2019-0719

Cited by 19 publications

(9 citation statements)

References 54 publications

(44 reference statements)

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“…However, we also observed no OS benefits through molecular subtypes. Treatments based on HER2-inhibitors showed a dramatic efficiency on BCBM of HER2+ diseases, with the greatest improvement obtained using tyrosine kinase inhibitors lapatinib, neratinib pyrotynib, and tucatinib [32][33][34][35]. In the HER2CLIMB randomized phase III trial, the combination of tucatinib with trastuzumab and capecitabine for patients with trastuzumabresistant MBC showed a 68% reduction of the risk of brain metastases progression or death (hazard ratio 0.32; 95% CI (0.22-0.48); p < 0.0001) [34].…”

Section: Discussionmentioning

confidence: 99%

Eribulin Efficacy on Brain Metastases in Heavily Pretreated Patients with Metastatic Breast Cancer

Sabatier

Martin

Vicier

et al. 2021

JCM

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The onset of brain metastases (BM) is a major turning point during advanced breast cancer (ABC) evolution, with only few treatment options when local therapies have failed. The therapeutic effect of eribulin, a wildly used drug in the treatment of ABC, remains unclear in this setting. Patients and Methods: We performed a retrospective observational study to assess eribulin efficacy in patients with ABC who displayed BM at time of eribulin initiation. We collected data from the medical files of all ABC patients who received eribulin at our institution from 2012 until 2020. Our main endpoint was the central nervous system (CNS) progression-free survival. (CNS-PFS). Other evaluation criteria were extra-cranial progression free survival (PFS) and overall survival (OS). Results: Twenty patients with BM monitoring data available were selected out of the 549 who received eribulin during the inclusion period. Fifteen patients (75%) had BM progressive as the best response, three patients (15%) had disease stabilization for more than 6 months and only one patient had a partial response according to RECIST 1.1 criteria. Median CNS-PFS was 3.39 months (95CI (3.02–3.76)). Cox univariate analysis identified molecular subtype as the only prognostic parameter in our cohort, with patients with hormone-receptor positive tumors less likely to experience CNS progression than those with triple-negative MBC (HR = 0.23 (95CI = 0.07–0.80), p = 0.021). Median extra-cranial PFS was 2.67 months (95CI (2.33–3.01)). Median OS was 7.68 months (95CI (0–17.41)). Conclusion: Eribulin seems to have only a limited impact on BM evolution. Hormone receptors expression may identify a subset of patients with better BM control.

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Section: Discussionmentioning

confidence: 99%

Eribulin Efficacy on Brain Metastases in Heavily Pretreated Patients with Metastatic Breast Cancer

Sabatier

Martin

Vicier

et al. 2021

JCM

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“…Neratinib is FDA-approved to treat HER2-positive metastatic breast cancer and is included in the ongoing biomarker-based INSIGhT trial for newly diagnosed unmethylated GB (NCT02977780) [ 423 ]. Neratinib showed adequate penetration of the BBB and efficacy against brain metastasis, with a biological half-life of 28 h [ 506 , 507 ]. Neratinib specifically binds the drug-binding cavity of ABCB1, thereby reducing drug efflux and enhancing drug sensitivity, particularly in the brain [ 508 ].…”

Section: Selection and Radiolabeling Of New Tkis For Trt Of Gbmentioning

confidence: 99%

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

et al. 2021

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Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up the scope for theranostic applications. In this review, the present status of RTKIs for the treatment, nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their potential to become new therapeutic GB radiopharmaceuticals.

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“…Neratinib (Figure 2), a 4-anilinoquinoline-based orally bioavailable kinase inhibitor, is an irreversible pan-ErbB inhibitor of EGFR, HER2, and HER4 targeting the intracellular domain, which results in reduced phosphorylation and downstream pathways activation. Neratinib has been recently FDA-and EMA-approved for the extended adjuvant treatment of early stage HER2-positive BC [32].…”

Section: Neratinibmentioning

confidence: 99%

Recent Advancements in the Development of Anti-Breast Cancer Synthetic Small Molecules

Elkaeed

Salam²,

Sabt³

et al. 2021

Molecules

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Among all cancer types, breast cancer (BC) still stands as one of the most serious diseases responsible for a large number of cancer-associated deaths among women worldwide, and diagnosed cases are increasing year by year worldwide. For a very long time, hormonal therapy, surgery, chemotherapy, and radiotherapy were used for breast cancer treatment. However, these treatment approaches are becoming progressively futile because of multidrug resistance and serious side effects. Consequently, there is a pressing demand to develop more efficient and safer agents that can fight breast cancer belligerence and inhibit cancer cell proliferation, invasion and metastasis. Currently, there is an avalanche of newly designed and synthesized molecular entities targeting multiple types of breast cancer. This review highlights several important synthesized compounds with promising anti-BC activity that are categorized according to their chemical structures.

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Neratinib: the emergence of a new player in the management of HER2+ breast cancer brain metastasis

Cited by 19 publications

References 54 publications

Eribulin Efficacy on Brain Metastases in Heavily Pretreated Patients with Metastatic Breast Cancer

Eribulin Efficacy on Brain Metastases in Heavily Pretreated Patients with Metastatic Breast Cancer

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

Recent Advancements in the Development of Anti-Breast Cancer Synthetic Small Molecules

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