Dr Patil emphasized the significance of the phase 3 CROWN trial (NCT03052608), which compared lorlatinib (Lorbrena) with crizotinib (Xalkori) in patients with ALK-positive metastatic NSCLC. With a hazard ratio of 0.19 (95% CI, 0.13-0.27) for progression-free survival, the trial demonstrated lorlatinib’s superior intracranial control and long-term efficacy compared with crizotinib, especially in patients with brain metastases. Drs Park and Patil also discussed challenges associated with managing lorlatinib-related toxicities, including mood changes, weight gain, and hyperlipidemia. Dr Patil suggested that starting at a lower dose and gradually escalating to the recommended dose could help mitigate some of these adverse effects and simultaneously maintain treatment efficacy.

The conversation concluded with a shift towards the broader application of targeted therapies in earlier disease stages, drawing parallels between the phase 3 ALINA study (NCT03456076) in patients with ALK-positive