Neuroprotective Rationale and Emerging Agents in ALK-Positive NSCLC

In this segment, faculty examine emerging data on the role of tropomyosin receptor kinase (TRK) activity in central nervous system disease, discussing a recent study evaluating TRK-inhibiting therapy in patients with leptomeningeal disease who lacked TRK alterations. The panel reviews how this activity may contribute to reductions in brain metastases and leptomeningeal disease. Discussion then turns to next-generation ALK inhibition, with faculty reviewing efficacy and safety data for a fourth-generation ALK inhibitor presented at ASCO, including activity across treatment-naive and pretreated cohorts, patients resistant to prior therapy, and those with on-target compound resistance mutations. The panel considers where such an agent may fit within the treatment continuum, how it compares against the high bar set by long-term frontline data, and the critical importance of biopsy at progression to distinguish ALK-based resistance from alternative mechanisms such as MET amplification.