Optimizing Treatment in EGFRm NSCLC With CNS Metastases: Multidisciplinary Management and Monitoring Strategies

This video segment discusses the management of patients with EGFR-mutated non–small cell lung cancer (NSCLC) with central nervous system (CNS) metastases, a common complication in both frontline and resistance settings. The discussion covers patients who present with symptomatic CNS metastases as well as those who are asymptomatic but found to have small brain metastases on initial brain MRI screening.

For patients with baseline brain metastases, clinicians strongly favor combination therapy approaches, particularly the osimertinib plus chemotherapy regimen (FLAURA2). This preference is based on clinical trial data showing that patients with baseline brain metastases were the primary beneficiaries of this combination, despite osimertinib already having significant CNS penetration and activity. The discussion emphasizes the importance of early multidisciplinary collaboration with radiation oncologists from treatment initiation, rather than making radiation decisions independently. Many patients with asymptomatic brain metastases can be managed without immediate radiation therapy, provided they receive close monitoring with repeat brain MRI scans as early as 4 weeks after starting treatment.

The approach to radiation therapy requires careful consideration, especially given the improving survival outcomes in EGFR-mutated NSCLC. While radiation remains an option for symptomatic patients, clinicians are increasingly cautious about long-term toxicities, including radiation necrosis that can develop years later and significantly impact quality of life. The segment concludes with a comparison between available combination regimens, noting that while both osimertinib-based combinations are reasonable first-line options, the FLAURA2 regimen (osimertinib plus carboplatin and pemetrexed) has the most compelling brain metastases data and is generally well tolerated, making it the preferred choice for patients with CNS involvement.