Sequencing After Progression on a Prior ROS1 Inhibitor

Martin Dietrich, MD, PhD, says the first move at progression is to extend frontline therapy rather than abandon it, looking for oligometastatic patterns that stereotactic radiation can handle while the inhibitor continues; a patient progressing at four years with two or three new lesions is a candidate. His second move is molecular, separating on-target from off-target resistance, since a new bypass pathway such as a KRAS alteration makes a second ROS1 inhibitor far less attractive. Dietrich favors biopsy of a progressing lesion and says the decision should follow molecular guidance rather than whichever agent is available. Wade Iams, MD, agrees outcomes are best when the most effective drug is used first, and manages oligoprogression while preserving central nervous system coverage. Ticiana Leal, MD, notes one approved agent is indicated only for pretreated patients.