How to Apply Research Developments in ALK-Positive NSCLC: With Chandler Park, MD, and Tejas Patil, MD

In the final episode of this 3-part Oncology Unplugged series, Chandler Park, MD, a genitourinary medical oncologist at Norton Cancer Institute in Louisville, Kentucky, and Tejas Patil, MD, an assistant professor of medical oncology at the University of Colorado School of Medicine in Aurora, discussed the evolving small cell lung cancer treatment paradigm. They also examined critical data that were presented at the 2024 ASCO Annual Meeting, focusing on treatment developments for patients with ALK-positive non–small cell lung cancer (NSCLC).

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 NSCLC and the phase 3 ADAURA study (NCT02511106) in patients with EGFR-mutated NSCLC. Dr Patil expressed interest in the future role of minimal residual disease (MRD) monitoring in these settings, suggesting that earlier interventions based on MRD status could help delay relapse and improve long-term outcomes for patients receiving TKIs.