Clinical Scorecard: Assessment of aumolertinib's safety and effectiveness in patients with EGFR-mutated non-small cell lung cancer and leptomeningeal metastasis: a retrospective analysis from a single center

At a Glance

Key Highlights

• Leptomeningeal metastasis occurs in 3–5% of NSCLC cases and up to 9.4% in EGFR-mutated patients, associated with poor prognosis and neurological decline
• Third-generation EGFR-TKIs, including aumolertinib, demonstrate improved CNS penetration and efficacy compared to first- and second-generation TKIs
• Aumolertinib showed prolonged progression-free survival and benefits in patients with CNS metastases in clinical trials, with promising real-world safety and effectiveness data

Guideline-Based Recommendations

Diagnosis

• Confirm LM diagnosis via positive cerebrospinal fluid cytology and/or typical contrast-enhanced MRI findings per EANO-ESMO guidelines
• Use genetic testing to identify classical EGFR mutations in NSCLC patients

Management

• Administer aumolertinib orally at 110 mg/day as standard dosing; dose escalation to 165 mg/day may be considered
• Consider aumolertinib for patients with EGFR-mutated NSCLC and LM, including those previously untreated or treated with other systemic therapies
• Evaluate treatment response using RECIST 1.1 for systemic lesions and RANO-LM criteria for leptomeningeal disease

Monitoring & Follow-up

• Perform imaging assessments every 2–3 months including brain MRI and, if clinically indicated, spinal MRI
• Monitor adverse events using CTCAE version 5.0 criteria
• Assess overall survival (OS), progression-free survival (PFS), and LM-specific PFS to evaluate treatment efficacy

Risks

• Potential adverse events related to EGFR-TKI therapy, with aumolertinib designed to minimize wild-type EGFR inhibition and associated toxicity
• Risk of disease progression despite treatment, necessitating close monitoring

Patient & Prescribing Data

79 patients with EGFR-mutated NSCLC and LM treated with aumolertinib in a single-center retrospective study

Majority (93.7%) started at 110 mg/day; 40.5% were treatment-naïve while 59.5% had prior systemic therapy; treatment responses assessed by RECIST 1.1 and RANO-LM criteria

Clinical Best Practices

• Use molecular testing to identify EGFR mutations prior to initiating targeted therapy
• Employ contrast-enhanced MRI and CSF cytology for accurate LM diagnosis and response evaluation
• Initiate aumolertinib promptly after LM diagnosis to maximize CNS disease control
• Regularly monitor neurological status and imaging to detect progression or adverse effects
• Adjust dosing based on tolerability and clinical response while minimizing toxicity

References

• European Association of Neuro-Oncology and European Society for Medical Oncology (EANO-ESMO) Clinical Practice Guidelines
• AENEAS Trial on Aumolertinib
• BLOOM Trial on Osimertinib in LM
• Retrospective Study Comparing Osimertinib and First-Generation EGFR-TKIs