Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models

Zhang, Yuhan; Zhang, Yaoshuai; Niu, Wenwen; Ge, Xianming; Huang, Fuhao; Pang, Jinlong; Li, Xian; Wang, Yu; Fan, Fangtian; Li, Shanshan; Líu, Hao

doi:10.3389/fphar.2021.750031

Cited by 34 publications

(31 citation statements)

References 42 publications

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“…These results indicate that aumolertinib is an effective third-generation EGFR TKI for patients with EGFR T790M-positive advanced NSCLC after disease progression following first- and second-generation EGFR TKI therapy ( 17 ). In the mouse model of NSCLC brain and spinal cord metastases, aumolertinib easily penetrates the blood-brain barrier and inhibits brain and spinal cord metastases ( 18 ). In the AENEAS study, aumolertinib, as a first-line treatment for locally advanced or metastatic EGFR-mutated NSCLC, achieved a PFS time of 19.3 months, which is marginally higher than the time of 18.9 months achieved with osimertinib in the FLAURA study ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

Aumolertinib challenge as an optional treatment in advanced non small‑cell lung cancer after osimertinib failure with epidermal growth factor receptor‑sensitive mutation: A case series

Ding

Leng

et al. 2022

Oncol Lett

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Osimertinib, as the first third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been recommended universally as the priority front-line therapeutic for advanced non-small cell lung cancer (NSCLC) carrying EGFR-sensitive mutations. However, patients inevitably acquire drug resistance to osimertinib. Aumolertinib is the second third -generation EGFR-TKI and has been similarly approved as a first-line treatment agent. The present study reports the cases of 3 patients who were challenged with aumolertinib after osimertinib failure. All 3 patients achieved a partial remission. The progression-free survival periods following aumolertinib were 10.0, 11 and 9.0 months (at the time of writing the study). Although the patient in case 2 succumbed to an intracerebral hemorrhage due to hypertension, aumolertinib remained effective as a treatment in cases 1 and 3. The present case series suggests the use of aumolertinib challenge as an optional treatment for patients with metastatic NSCLC harboring EGFR-sensitive mutations after osimertinib failure. The therapeutic strategy of switching from osimertinib to aumolertinib is worth exploring further in the near future.

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Section: Discussionmentioning

confidence: 99%

Aumolertinib challenge as an optional treatment in advanced non small‑cell lung cancer after osimertinib failure with epidermal growth factor receptor‑sensitive mutation: A case series

Ding

Leng

et al. 2022

Oncol Lett

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“…However, novel EGFR-TKIs with proven efficacy in CNS are clinically needed. Pharmacokinetic studies in mice showed that almonertinib, a novel third gen TKI, has a good BBB penetration ability [232], and early clinical evidence of almonertinib activity in a patient with advanced EGFRm NSCLC and BMs has been reported, showing intracranial and extracranial response [232].…”

Section: Open Questions In Treatment Strategiesmentioning

confidence: 99%

EGFR signaling pathway as therapeutic target in human cancers

Maroni

Tenen

2022

Seminars in Cancer Biology

133

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“…107,118,119 In contrast, the third-generation EGFR-TKIs osimertinib, almonertinib, and lazertinib have good bloodbrain barrier penetration. [120][121][122] Compared with first-generation EGFR-TKIs, upfront osimertinib resulted in improved CNS outcomes. 119 These data support osimertinib as upfront treatment in this setting.…”

Section: Systemic Treatment Of Nsclc Brain Metastasesmentioning

confidence: 99%

Emerging Systemic Treatment Perspectives on Brain Metastases: Moving Toward a Better Outlook for Patients

Alvarez‐Breckenridge

Remón

Piña

et al. 2022

American Society of Clinical Oncology Educational Book

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The diagnosis of brain metastases has historically been a dreaded, end-stage complication of systemic disease. Additionally, with the increasing effectiveness of systemic therapies that prolong life expectancy and improved imaging tools, the incidence of intracranial progression is becoming more common. Within this context, there has been increasing attention directed at understanding the molecular underpinnings of intracranial progression. Exploring the unique features of brain metastases compared with their extracranial counterparts to identify aberrant signaling pathways, which can be targeted pharmacologically, may help lead to new treatments for this patient population. Additionally, critical discoveries outside the sphere of the central nervous system are increasingly being applied to brain metastases with the emergence of immune checkpoint inhibition, becoming a prevalent treatment option for patients with brain metastases across multiple histologies. As novel treatment strategies are considered, they require thoughtful incorporation of agents that can cross the blood-brain barrier and can synergize with pre-existing agents through rational combinations. Lastly, as clinicians and scientists continue to understand key molecular features of these tumors, they will continue to influence the treatment algorithms that are developing for the management of these patients. Due to the complexity of treatment decisions for patients with brain metastases, an emerging tool is the utilization of multidisciplinary brain metastasis tumor boards to ensure optimal treatment decisions are made and that patients are provided access to applicable clinical trials. Looking to the future, the collective effort to understand the various tumor-intrinsic and tumor-extrinsic factors that promote central nervous system seeding and propagation will have the potential to change the clinical trajectory for these patients.

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Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models

Cited by 34 publications

References 42 publications

Aumolertinib challenge as an optional treatment in advanced non small‑cell lung cancer after osimertinib failure with epidermal growth factor receptor‑sensitive mutation: A case series

Aumolertinib challenge as an optional treatment in advanced non small‑cell lung cancer after osimertinib failure with epidermal growth factor receptor‑sensitive mutation: A case series

EGFR signaling pathway as therapeutic target in human cancers

Emerging Systemic Treatment Perspectives on Brain Metastases: Moving Toward a Better Outlook for Patients

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