Case Presentation: Mrs. Chen, a 58-Year-Old Never-Smoker With EGFR-Mutant NSCLC and a TP53 Co-Mutation

Dr. Matthew Gumbleton introduces the case of Mrs. Chen, a 58-year-old Asian woman and never-smoker who presents with progressive shortness of breath and about 10 pounds of unintentional weight loss over 2 months. She works full time as a high school teacher and lives about 75 minutes from the nearest oncology clinic. Her medical history is notable for hypertension on amlodipine and hypothyroidism on levothyroxine. She has no significant cardiac, liver, or kidney disease and no history of blood clots. Her Eastern Cooperative Oncology Group (ECOG) performance status is 1, limited primarily by her shortness of breath.

Computed tomography (CT) of the chest demonstrates a large right upper lobe mass, significant mediastinal lymphadenopathy, and contralateral lung involvement. Biopsy confirms stage IVA non-squamous NSCLC (adenocarcinoma), and magnetic resonance imaging (MRI) of the brain shows no central nervous system (CNS) involvement. Comprehensive tissue next-generation sequencing (NGS) identifies an EGFR exon 19 deletion and a TP53 R248W pathogenic co-mutation, with no other relevant alterations.

Mrs. Chen's goals of care drive the treatment conversation. She wants to minimize time away from work, does not want treatment side effects to limit her ability to teach, and wants to maximize her chance of long-term survival and durable response. She expresses interest in a chemotherapy-free regimen if possible.

In the next episode, “Weighing the Three Preferred First-Line Options Against Mrs. Chen's Goals of Care,” Dr. Gumbleton frames how osimertinib monotherapy, amivantamab plus lazertinib, and osimertinib plus chemotherapy each align with her priorities.