Case Presentation — Mr. Smith, a 53-Year-Old Man With EGFR-Mutant NSCLC and Brain Metastases

Dr. Estelamari Rodriguez introduces the case of Mr. Smith, a 53-year-old man who presents with new-onset headaches and a witnessed seizure. He is a former light smoker (5 pack-year, quit 15 years ago) with type 2 diabetes and no hepatic, renal, or cardiac impairment, no history of venous thromboembolism (VTE), and an Eastern Cooperative Oncology Group (ECOG) performance status of 1.

Brain magnetic resonance imaging (MRI) reveals 4 enhancing parenchymal brain metastases (largest 1.8 cm, right frontal lobe) with mild surrounding edema. Computed tomography (CT) of the chest, abdomen, and pelvis shows a 3.5 cm left lower lobe mass with contralateral pulmonary nodules and bilateral adrenal metastases. Biopsy confirms stage IVB non-squamous non-small cell lung cancer (NSCLC) (adenocarcinoma), and comprehensive tissue next-generation sequencing (NGS) identifies an EGFR exon 21 L858R substitution mutation, no TP53 co-mutation, and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of 10%. Mr. Smith is started on dexamethasone and levetiracetam; neurosurgery and radiation oncology are consulted. He wants to protect brain function and independence, cannot drive due to seizure precautions, and lives 45 minutes from clinic, with his part-time-working wife as caregiver.

Dr. Rodriguez then reviews the three first-line options: osimertinib monotherapy, amivantamab plus lazertinib, and osimertinib plus platinum/pemetrexed chemotherapy. She notes that up to 70% of patients with EGFR-mutant NSCLC develop brain metastases during the disease course, making durable CNS control a critical treatment goal.

In the next episode, “Comparing CNS Efficacy of First-Line Regimens in EGFR-Mutant NSCLC With Brain Metastases,” Dr. Rodriguez walks through the intracranial data from the MARIPOSA and FLAURA2 trials.