Standard-dose osimertinib for refractory leptomeningeal metastases in T790M-positive EGFR-mutant non-small cell lung cancer.

Abstract

BACKGROUND:

Osimertinib demonstrated promising efficacy for refractory leptomeningeal metastases (LM) in preclinical data and a clinical study at 160 mg, but there is limited data for the standard 80 mg dose.

METHODS:

T790M-positive patients with suspected LM after classical epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) failure were enroled.

RESULTS:

We investigated 13 patients (5 definitive and 8 possible LM cases). In two of the five definitive cases with T790M in and outside the central nervous system (CNS), osimertinib was effective for both lesions, with cerebrospinal fluid (CSF) clearance of cancer cells and sensitive/T790M mutations. In three definitive cases with extra-CNS T790M without CSF T790M, cancer cells and sensitive mutations in the CSF persisted after osimertinib initiation. The median progression-free survival of all 13 patients was 7.2 months. Osimertinib was generally well-tolerated despite poor performance status, but interstitial lung disease (grade 2) was confirmed in one patient. Based on 25 samples from 13 patients, the osimertinib CSF penetration rate was 2.5±0.3%.

CONCLUSIONS:

Osimertinib 80 mg is a useful therapeutic option for refractory LM after classical EGFR-TKI failure. It appears more effective in CSF T790M-positive cases.

• Authors: Shigeki Nanjo, Akito Hata, Chiyuki Okuda, Reiko Kaji, Hideaki Okada, Daisuke Tamura, Kei Irie, Hiroshi Okada, Shoji Fukushima, Nobuyuki Katakami
• Journal: British journal of cancer (Br J Cancer) Vol. 118 Issue 1 Pg. 32-37 (01 2018) ISSN: 1532-1827 [Electronic] England
• PMID: 29190637 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acrylamides
• Aniline Compounds
• Piperazines
• Protein Kinase Inhibitors
• osimertinib
• EGFR protein, human
• ErbB Receptors

Topics

• Acrylamides
• Aged
• Aniline Compounds
• Carcinoma, Non-Small-Cell Lung (cerebrospinal fluid, drug therapy, genetics)
• ErbB Receptors (cerebrospinal fluid, genetics)
• Humans
• Lung Diseases, Interstitial (chemically induced, epidemiology)
• Lung Neoplasms (cerebrospinal fluid, drug therapy, genetics)
• Meningeal Neoplasms (cerebrospinal fluid, drug therapy, genetics, secondary)
• Middle Aged
• Mutation
• Pilot Projects
• Piperazines (administration & dosage, adverse effects, cerebrospinal fluid)
• Progression-Free Survival
• Prospective Studies
• Protein Kinase Inhibitors (administration & dosage, adverse effects, cerebrospinal fluid)
• Treatment Outcome