Ways found to save patients with meningeal metastatic EGFR-mutant lung cancer

Patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) that has metastasized to the meninges have a short life expectancy of only a few weeks to a few months.

However, a Korean medical team has come up with a way to help them live longer.

Osimertinib, a third-generation targeted anticancer drug, has been shown to improve the prognosis of patients with EGFR-mutant lung cancer that has metastasized to the meninges by increasing their response to treatment and prolonging their survival, even at a standard dose of 80 mg once a day.

Samsung Medical Center said Monday that a research team led by Professors Ahn Myung-ju and Park Se-hoon of the Department of Hematology-Oncology and Professor Lee Jung-il of the Department of Neurosurgery confirmed the clinical efficacy of the third-generation TKI inhibitor osimertinib in patients with EGFR-mutant NSCLC with meningeal metastases.

The most common EGFR mutations in NSCLC are treated with tyrosine kinase inhibitors (TKIs) as first-line therapy. First- and second-generation TKI inhibitors, which are often used due to reimbursement issues, are prone to frequent resistance and poor blood-brain barrier penetration, which can lead to metastasis to the meninges. To address this, physicians attempted to increase the dose of the drug to cross the blood-brain barrier but faced limitations due to potential increases in side effects.

That explains why the team turned to osimertinib, a third-generation TKI inhibitor designed to penetrate the blood-brain barrier more easily than previous generations of TKI inhibitors, so the researchers believed that a reduced dose would be sufficient to achieve clinical effects.

The researchers recruited 73 patients with NSCLC between November 2020 and November 2022 at six medical institutions, including Samsung Medical Center, to conduct the phase 2 BLOSSOM study. All patients had EGFR mutations and had previously been treated with first- or second-generation TKIs but had developed meningeal metastases with resistance.

The team treated them with 80 mg of osimertinib daily for 28 days and monitored their progress. As of October 2023, the median follow-up was 15.6 months, with 15 patients still receiving treatment, according to the team. This is encouraging compared to the short life expectancy for patients with meningeal metastases, which is only a few weeks to a few months.

The objective response rate (ORR) was 51.6 percent, and the disease control rate (DCR) was 81.3 percent. Progression-free survival (PFS) was 11.2 months and response rate was 12.6 months.

Only 57.5 percent of patients experienced osimertinib-related side effects, including such mild ones as itching (13.7 percent) and rash (12.3 percent), thanks to the reduced drug concentration, the researchers said.

"It is very promising to see a survival of more than one year in patients with meningeal metastases who had very limited treatment options, demonstrating effective treatment," Professor Park said.

Professor Ahn said, "It is encouraging that we have achieved clinically meaningful results in Korean lung cancer patients with EGFR mutations, allowing more patients to be treated. “We have provided a scientific basis for treating patients with hard-to-treat meningeal metastases."