Case 1, Brain Metastases and TP53 Co-Mutation

Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center presents a 68-year-old woman with newly diagnosed metastatic lung adenocarcinoma, an epidermal growth factor receptor (EGFR) exon 19 deletion with a concurrent TP53 co-mutation, multiple small asymptomatic brain metastases on staging magnetic resonance imaging, disease confined to lung and brain, and good performance status with support at home. Siddhartha Devarakonda, MD, of Providence Swedish Cancer Institute treats the combination of risk factors rather than any single one as the driver, and is comfortable recommending combination therapy, leaving the choice between a chemotherapy-based and an amivantamab-based regimen. He notes that retrospective TP53 data were mixed, that the MARIPOSA subset analysis shows benefit with the combination, and that randomized data also support osimertinib plus chemotherapy, so the decision returns to toxicity and to what the treating team can manage safely. He adds that an exon 19 deletion is relatively favorable for single-agent therapy.