Lorlatinib as first-line therapy for ALK-positive advanced non-small cell lung cancer: A retrospective, multicenter, real-world study from China.

e20740 Background: The evolution of ALK tyrosine kinase inhibitors (TKIs) has led to significantly prolonged survival in patients with ALK-positive advanced non-small cell lung cancer (NSCLC). Notably, in the phase III CROWN study, the median progression-free survival (PFS) for the third-generation ALK TKI lorlatinib remained unreached after 5 years of follow-up. Currently, published real-world evidence on lorlatinib primarily focuses on its efficacy and safety in later-line therapy, and a significant gap exists in real-world data for lorlatinib as a first-line therapy. Therefore, we conducted this retrospective, multicenter, single-arm, real-world study in Zhejiang Province, China. Methods: This retrospective, multicenter, single-arm study enrolled adult patients with histologically or cytologically confirmed ALK-positive advanced NSCLC receiving first-line lorlatinib therapy from 2022 to 2025. Patient data were collected from institutional Electronic Medical Record (EMR) systems by investigators. The primary endpoint was PFS. Secondary endpoints included disease control rate (DCR), objective response rate (ORR), intracranial ORR, and safety. Results: As of the cutoff date, a total of 82 eligible patients with ALK-positive advanced NSCLC were included in this analysis. The median age was 52 (range: 26–86), 48.8% were female, 78.0% were never-smokers, 96.3% had adenocarcinoma histology, and 20.7% had baseline brain metastasis. The median follow-up of 15.07 months (95% CI: 10.77–19.36). The median PFS for first-line lorlatinib in patients with ALK-positive advanced NSCLC has not yet been reached (95% CI: NR–NR). The 12-month PFS rate was 96.1% (with baseline brain metastasis: 73.2%; without baseline brain metastasis: 100%). The ORR was 70.8% among evaluable patients (n = 72), with a 100% DCR and 92.9% intracranial ORR. The most common treatment-emergent adverse events (TEAEs) were hypertriglyceridemia (80.5%) and hypercholesterolemia (80.5%). The incidence of grade 3–4 TEAEs was 31.7%, which was predominantly comprised of hypertriglyceridemia (22.0%) and hypercholesterolemia (7.3%). No treatment-related deaths were reported. Conclusions: Lorlatinib demonstrated potent efficacy in the first-line treatment of Chinese patients with ALK-positive advanced NSCLC, achieving a 12-month PFS rate of 96.1% regardless of baseline brain metastasis status, with a safety profile consistent with the CROWN study. The most common grade 3–4 adverse events were hypertriglyceridemia and hypercholesterolemia. The study is ongoing, with plans to further expand the sample size and conduct long-term follow-up.