Defining High-Risk Disease and Outcomes With Brain Metastases

Siddhartha Devarakonda, MD, of Providence Swedish Cancer Institute pushes back on the high-risk label in epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC), noting that when 89% of patients with analyzable circulating tumor DNA in the phase 3 MARIPOSA study carry at least 1 high-risk feature, the term loses meaning. His practical read is that the remaining 11% may be the patients who can reasonably receive single-agent tyrosine kinase inhibitor therapy. Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center presents median progression-free survival of 18.3 months with amivantamab plus lazertinib versus 13.0 months with osimertinib among patients with brain metastases. Matthew Gumbleton, MD, PhD, of Huntsman Cancer Institute treats lung cancer as high risk regardless, arguing that responses in the brain are achievable but durability is the real question, and that avoiding later radiation matters for long-term quality of life.