Complete Remission of Multiple Brain Metastases in a Patient with EGFR-Mutated Non-Small-Cell Lung Cancer Treated with First-Line Osimertinib without Radiotherapy

Abstract

Osimertinib has demonstrated efficacy against stable or asymptomatic central nervous system (CNS) metastases of epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) in phase 2 and 3 clinical trials that allowed prior CNS radiotherapy. However, the efficacy of osimertinib only or the optimal treatment combination or sequence of radiotherapy has not been investigated. A 74-year-old woman diagnosed with T4N1M1c Stage IVB lung adenocarcinoma with EGFR mutation presented with a left upper lobe mass and multiple bilateral lung metastases. A total of more than 20 asymptomatic multiple brain metastases with a maximum diameter of 12 mm were diagnosed simultaneously. Osimertinib was administered as first-line treatment. Whole brain radiotherapy was deferred because she had no neurological symptoms. After 5 weeks, the multiple brain metastases disappeared completely, together with the response in the lung lesions. This case demonstrated that first-line treatment with osimertinib could even achieve complete remission of multiple brain metastases comprising as many as twenty lesions of EGFR-mutated NSCLC without radiation therapy. Radiation therapy for brain metastases can be deferred or even withheld. A new treatment strategy for EGFR mutated NSCLC with CNS metastases should be investigated using osimertinib, especially regarding optimal combination or sequence of radiotherapy.

Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT

“…Similar results supported that WBRT should be deferred or even withheld in another recent case report. Authors suggested that a multiple asymptomatic BM patient with EGFRm NSCLC treated with first-line osimertinib without RT reached iCR with the response of lung lesions (Ameku and Higa 2020 ). A case published in 2023 also reported an EGFRm NSCLC patient with symptomatic BM getting iCR after aumolertinib monotherapy (Shan et al 2023 ).…”

Osimertinib in EGFR-Mutated Lung Cancer: A Review of the Existing and Emerging Clinical Data

“… 41 When it comes to earlier generation TKIs, their concentration within the cerebrospinal fluid is less than that found in the blood which in turn results in treatment failure due to pharmacokinetic limitations. 42 Osimertinib, on the other hand, effectively penetrates the blood-brain barrier, resulting in higher brain exposure than the previously tested EGFR- TKIs. A positron emission tomography (PET) study with radio-isotope labeled osimertinib showed that the drug rapidly distributed within the brain, with a higher uptake into the grey compared to the white matter with a Tmax of 13 minutes (range 5–30min).…”

“…41 When it comes to earlier generation TKIs, their concentration within the cerebrospinal fluid is less than that found in the blood which in turn results in treatment failure due to pharmacokinetic limitations. 42 Osimertinib, on the other hand, effectively penetrates the blood-brain barrier, resulting in higher brain exposure than the previously tested EGFR-TKIs.…”

The value of disease-free survival (DFS) and osimertinib in adjuvant non-small-cell lung cancer (NSCLC): an international Delphi consensus report

“… 15 Recent studies have indicated a role for next-generation EGFR-TKIs, such as osimertinib, in the treatment of CNS metastases. 16 Osimertinib is a third-generation EGFR-TKI approved in many countries around the world for first-line EGFRm advanced NSCLC and EGFR T790M mutation-positive advanced NSCLC, 17 , 18 and is now recommended as the preferred EGFR-TKI in guidelines, in part due to its proven CNS efficacy. In the recent ADAURA trial, adjuvant osimertinib reduced the risk of disease recurrence or death by 80% for stage IB-IIIA patients [hazard ratio (HR) 0.20; 99.12% confidence interval (CI) 0.14-0.30; P < 0.001] compared to a placebo.…”