ArticleNeuro-oncology advances
Dose escalation of osimertinib for intracranial progression in EGFR mutated non-small-cell lung cancer with brain metastases.
Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- High-dose furmonertinib as first-line treatment for untreated EGFR-mutated advanced NSCLC with central nervous system metastases: A phase 2 trial.Cell reports. Medicine · 2026Trial
- ErbB signaling in brain injury regeneration: Pathway interactions and therapeutic potential.Neural regeneration research · 2026Article
- EGFR-TKI monotherapy versus combination therapy as first-line treatment for EGFR-mutant NSCLC with brain metastases: a real-world comparison analysis.BMC cancer · 2026Article
- Decoding Brain Metastasis With Liquid Biopsy: Biomarkers and Technologies in EGFR-Mutant NSCLC.Cancer medicine · 2026Review
- Craniocerebral radiotherapy for EGFR-mutant non-small cell lung cancer with brain metastasis: Current evidence and future perspectives on therapeutic strategies (Review).Molecular and clinical oncology · 2025Article
- Survival Outcomes in EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases: Kaplan-Meier and Cox Regression Analyses Across Treatment Stages.The clinical respiratory journal · 2025Article
- Integrated PBPK-EO modeling of osimertinib to predict plasma concentrations and intracranial EGFR engagement in patients with brain metastases.Scientific reports · 2024Article
- Efficacy and Safety of Dose-Escalated Alectinib in Patients With Metastatic ALK-Positive NSCLC and Central Nervous System Relapse on Standard-Dose Alectinib.JTO clinical and research reports · 2024Article
- Central nervous system efficacy of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small cell lung cancer: a pooled analysis from two phase 2 studies.BMC medicine · 2023Article
- Advances in the Management of Central Nervous System Metastases in Non-Small Cell Lung Cancer.Cancers · 2023Review
- Osimertinib for EGFR-Mutant Non-Small-Cell Lung Cancer Central Nervous System Metastases: Current Evidence and Future Perspectives on Therapeutic Strategies.Targeted oncology · 2023Review
- Article
- Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance.Journal of hematology & oncology · 2022Review
- [Consensus on Application of Third-generation EGFR-TKI in EGFR Mutated NSCLC (2022 Version)].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Article
- Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management.Nature reviews. Clinical oncology · 2022Review
- High-Dose Osimertinib for CNS Progression in EGFR+ NSCLC: A Multi-Institutional Experience.JTO clinical and research reports · 2022Article
- Epidermal growth factor receptor mutations and brain metastases in non-small cell lung cancer.Frontiers in oncology · 2022Review
- Real-world efficacy and safety of mobocertinib inFrontiers in oncology · 2022Article
- Osimertinib in advanced EGFR-mutant lung adenocarcinoma with asymptomatic brain metastases: an open-label, 3-arm, phase II pilot study.Neuro-oncology advancesArticle
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOsimertinib is a selective irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) with increased penetration across the blood-brain barrier compared with previous EGFR-TKIs, and thus, a 52% reduction in the risk of intracranial disease progression is seen when it is used as a first line of therapy compared with gefitinib and erlotinib. It is also efficient as second-line therapy for patients who developed the T790M resistance mutation following treatment with previous generation TKIs. Here, we report 11 patients who were treated by an increasing dose of osimertinib from 80 mg to 160 mg QD orally following intracranial progression in either first- or second-line setting.
methodsThis is a subcohort analysis from a larger nonrandomized, phase 2, open-label trial, evaluating the efficacy of osimertinib dose escalation from 80 mg to 160 mg in EGFR-mutated advanced non-small-cell lung cancer (NSCLC) patients with intracranial progression in either first- (arm A) or second-line setting (arm B for T790M+ and C for T790M-).
resultsEleven patients, 5 in arm A, 4 in arm B, and 2 in arm C were reported in this study. The mPFS of osimertinib before dose escalation was 11.4 ± 8.9 (6.6-30.7) months for arm A, 8.7 ± 1.8 (6.3-11.2) for arm B, and 14.5 ± 7.8 (6.7-22.3) for arm C. Intracranial response rate to dose escalation was 54% (6 of 11) with 2 of 11 having intracranial stability. Median iPFS was 4.3 ± 7.4 (0.7-25.5) months; 3.8 ± 6.4 (1.8-18.9), 5.6 ± 9.7 (0.7-25.5), and 7.0 ± 2.7 (4.3-9.6) for arms A/B/C, respectively. Dose escalation was well tolerated with diarrhea and paronychia as the main dose-limiting symptoms.
conclusionsOsimertinib 160 mg is feasible and may offer a therapeutic alternative for patients with isolated intracranial progression on osimertinib standard (80 mg) dose. Further studies on CNS osimertinib pharmacokinetics are needed to test this hypothesis.
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