Acquired Resistance Mechanisms After First-Line Therapy

Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center presents long-term resistance data from the phase 3 MARIPOSA study in epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC), where amivantamab plus lazertinib reduced acquired MET amplification approximately fourfold and secondary EGFR resistance mutations approximately fivefold compared with osimertinib. Matthew Gumbleton, MD, PhD, of Huntsman Cancer Institute says closing off common escape routes matters for durability, since MET amplification recurs across oncogene-driven subtypes. Dr Rodriguez notes that repeat biopsies at progression often fail to explain why a patient progressed, which makes covering more up front appealing. Siddhartha Devarakonda, MD, of Providence Swedish Cancer Institute cautions that every treatment alters biology and that the open question is which escape routes emerge and whether they can be blocked, concluding that the jury is still out on whether altering biology up front translates into longer survival.