Clinical efficacy analysis of Osimertinib treatment for a patient with leptomeningeal metastasis of EGFR+ non-small cell lung cancer without the T790M mutation

Abstract

Background: To find the method of therapy of leptomeningeal metastasis (LM) to non-small cell lung cancer (NSCLC) patient with EGFR mutation (EGFR+) but without T790M mutation.Methods: A retrospective analysis was reviewed for 5 NSCLC patients with EGFR+ who develop to LM from January 2018 to February 2019 in our hospital.Results: All five NSCLC cases were adenocarcinoma, four cases were verified existed EGFR mutation with 19 exon deletion in the first diagnosed by biopsy tissue, the other tissue was verified 21 exon mutation. Two cases were initially diagnosed with LM, and the other three cases were found metastasis with leptomeningeal respectively after 64, 3 and 4 months when the lung cancer was diagnosed. There were not verified to exist T790M mutation with EGFR+ when all the five cases developed to LM. The major symptom was headache and blurred vision. In the image scanning, two cases were not revealed, but other three cases show that multiple metastatic lesions with brain and meninges. All patients were identified existed adenocarcinoma cells in cerebrospinal fluid (CSF). Four cases were treated by the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and joint therapy including chemotherapy and radiotherapy, and the other case was treated by temozolomide and intrathecal chemotherapy in their earlier therapy. The curative effect was significant when they took osimertinib orally 80 mg once a day, for the disease progressing. The neurological symptoms were relieved in patient about 5-10 days after osimertinib treatment. The remission time was 10, 7, 7, 5, 4 months respectively until last following time to June 2019. The survival time was respectively 74, 7, 27, 18, and 4 months. The side effects were not increased.Conclusions: Whether EGFR+ with T790M mutation was positive or negative, osimertinib is an effective drug and can improve quality of life and prolong the survival for NSCLC patient with EGFR mutation to progress LM.

Epidermal growth factor receptor-Mutated Non-small-cell Lung Cancer with Intracranial Progressions and Stable Extracranial Diseases Benefit from Osimertinib Regardless of T790M Mutational Status

“…It has been reported that osimertinib showed good efficacy in pretreated EGFRm NSCLC patients with LM regardless of their T790M status. 14,15 In our study, osimertinib displayed optimal efficacy in pretreated patients with BM irrespective of their T790M mutational status from plasma genotyping. Two explanations should be considered.…”

“…No statistical difference in PFS and iPFS was found between patients with evaluable intracranial lesions and those with unevaluable intracranial lesions (median PFS: 8.0 months [95% CI: 5. 15 4A and 4B). DCR for extracranial lesions and overall lesions were 100.0%, 66.7%, and 87.5% for patients with T790M, no T790M, and unknown T790M mutational status, respectively (P=.165) (Table 2).…”

MUSASHI‐2 confers resistance to third‐generation EGFR‐tyrosine kinase inhibitor osimertinib in lung adenocarcinoma

“…It shows less serious adverse events and high efficacy compared with the first‐ and second‐generation EGFR‐TKIs 5 . NSCLC patients with the EGFR‐T790 M mutation 13,14 and even without the T790M mutation, 15 benefit from osimertinib treatment. However, similar to earlier generations of EGFR‐TKIs, acquired resistance to osimertinib remains a major challenge.…”

“…[7][8][9] Osimertinib (AZD9291) is a third-generation irreversible oral EGFR-TKI that potently inhibits both EGFR-activating mutations and T790 M. [10][11][12] It shows less serious adverse events and high efficacy compared with the first-and second-generation EGFR-TKIs. 5 NSCLC patients with the EGFR-T790 M mutation 13,14 and even without the T790M mutation, 15 benefit from osimertinib treatment.…”

Efficacy and safety of domestic and imported gefitinib in patients with advanced non-small cell lung cancer

“…With the discovery of certain signal transduction pathways in tumor cell growth, new treatment targets have become a research focus. Epidermal growth factor receptor (EGFR) dependent pathways have become important targets in treatment of NSCLC (5). In many solid tumors, EGFR overexpression has been found to be associated with a poor prognosis, a short survival time, and an increased likelihood of tumor metastasis.…”