Weighing CNS Activity and Co-Mutations in Frontline Selection

Edgardo Santos, MD, FACP, FASCO, of Starling Oncology, describes which elements of the first-line data carry the most weight in his practice when he treats EGFR-mutated advanced non–small cell lung cancer. He tells Wade Iams, MD, MSCI, of Tennessee Oncology, that both the FLAURA2 regimen of platinum-based chemotherapy plus osimertinib and the MARIPOSA regimen of amivantamab plus lazertinib improved overall survival over osimertinib alone, which he treats as the starting point of any discussion. Dr Santos then walks through the higher-risk features both trials examined: brain metastases, TP53 co-mutation, bone metastases, liver metastases, detectable circulating tumor DNA (ctDNA) at baseline, and failure to clear ctDNA on therapy. In his own clinic he focuses on 2 of these, brain metastases and TP53 co-mutation, and looks for a regimen with durable central nervous system activity when brain disease is present. He returns to overall survival as the measure that matters most to patients.