Clinical Case 1 Continued: Frontline Treatment Selection and Monitoring in ROS1-Positive Advanced Non-Small Cell Lung Cancer

All panelists select lorlatinib at 600 mg for this patient based on response rates, duration of disease control, favorable tolerability, and its design intent to achieve superior CNS penetration compared to earlier-generation ROS1 inhibitors, which is particularly relevant given the patient's age, symptomatic disease burden, and risk of future CNS progression. For patients with baseline brain metastases, the panelists confirm they would also choose lorlatinib based on data showing intracranial response rates of approximately 68% in the first-line setting and meaningful second-line CNS responses as well, reducing reliance on radiation and its long-term neurocognitive consequences.

NP Hernandez describes monitoring: baseline ECG (given QTc prolongation risk), complete metabolic panel and complete blood count before each treatment cycle, and close early follow-up every two weeks for the first 6 weeks to identify and proactively manage adverse events including transaminase elevation, diarrhea (typically early-onset, transient, and grade 1-2), and nausea. She stresses that patients should receive antiemetics as needed from the outset. Grade 1 diarrhea should not be equated with grade 3 toxicity; recognizing typical onset and duration and not conflating severity categories is essential for appropriate toxicity management and avoiding unnecessary discontinuation.

Dr. Pellini emphasizes dose reductions are feasible without compromising efficacy and should be used proactively rather than reactively. The panel advocates for a team-based approach by bringing all team members including nurses, pharmacists, and nurse practitioners to the first appointment to build patient trust, distribute education responsibilities, and ensure comprehensive follow-up across high-volume practices.