Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study.
Leptomeningeal metastases (LM), associated with poor prognosis, are frequent complications of advanced non-small cell lung cancer (NSCLC) patients, especially in patients with epidermal growth factor receptor (EGFR) mutations.
EGFR mutations in the plasma or CSF were detected in 6/11 (54.5%) and 5/10 (50%) BM patients, and in 4/11 (36.4%) and 9/12(75%) LM patients, respectively.
After 8 months, she experienced disease progression with leptomeningeal metastasis and switched to osimertinib based on an acquired EGFR T790 M mutation.
Notably, NGS of CSF was superior to genetic testing of peripheral blood at identifying an uncommon EGFR mutation (G719A) in a patient with NSCLC and leptomeningeal metastases.
We report here a case of osimertinib used at 160 mg once daily in a heavily pretreated patient with EGFR exon 20 T790M-negative advanced NSCLC with LM to achieve a partial response, including shrinkage of the LM, for up to 12 months until further progression.
EGFR-mutant NSCLC patients with LM, who had previously received treatment at the Shandong Cancer Hospital and Institute from July 2014 to March 2018 were reviewed retrospectively.
LMs were more frequent in driver gene-mutated patients, and cerebrospinal fluid (CSF) cell-free DNA has shown unique genetic profiles of LM in EGFR-mutated LM.
However, the underlying mechanisms of the metastasis process are still poorly understood.<b>Experimental Design:</b> We performed next-generation panel sequencing of primary tumor tissue, cerebrospinal fluid (CSF), and matched normal controls from epidermal growth factor receptor (<i>EGFR</i>) mutation-positive NSCLC patients with LM.<b>Results:</b> The status of <i>EGFR</i>-activating mutations was highly concordant between primary tumor and CSF.
The combination of bevacizumab and erlotinib could be an optional effective management strategy for patients with LMs from NSCLC and harboring EGFR-mutation.
For those with "oncogene addiction," new generation epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) were developed to strongly penetrate the blood-brain barrier (BBB) with the aim to prevent central nervous system cancer dissemination, eventually impacting on LM appearance and its subsequent management.
Prior to routine EGFR mutation testing, surgical resection, stereotactic radiosurgery and/or whole brain radiation therapy (WBRT) were the main treatment options whereas treatment options for patients with leptomeningeal metastases (LM) included intra-thecal chemotherapy, WBRT, and ventriculo-peritoneal shunting.
In the dose-expansion phase, AZD3759 at 200 mg or 300 mg twice a day was administered to patients with either brain or leptomeningeal metastases who had never received an EGFR tyrosine kinase inhibitor and patients with leptomeningeal metastases who had been pretreated with an EGFR tyrosine kinase inhibitor.