Lorlatinib versus crizotinib as first-line treatment for advanced ALK-positive non-small-cell lung cancer: 7-year update from the phase III CROWN study
Year: 2026
Type: article
Abstract: BACKGROUND: Due to the unprecedented progression-free survival (PFS) benefit with lorlatinib after 5 years of follow-up in the phase III CROWN study, we aimed to quantify long-term outcomes at 7 years. PATIENTS AND METHODS: Treatment-naive patients (N = 296) with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) were randomly assigned 1:1 to receive lorlatinib 100 mg once a day (n = 149) or crizotinib 250 mg twice a day (n = 147). This post hoc analysis presents investigator-assessed efficacy outcomes, safety, and biomarker analyses. RESULTS: With a median follow-up of 83.0 and 77.2 months, median PFS was not reached (NR) with lorlatinib [95% confidence interval (CI), 68.5-NR] and was 9.1 months (95% CI 7.4-10.9) with crizotinib [hazard ratio (HR) 0.19, 95% CI 0.13-0.26]; 7-year PFS was 55% and 3%, respectively. With lorlatinib, patients without a PFS event at the end of 24 months had a 79% probability of survival without progression at year 7. No new intracranial progression events occurred after the first 30 months on lorlatinib. Median time to intracranial progression was NR (95% CI NR-NR) with lorlatinib and 16.4 months (95% CI 12.7-21.9) with crizotinib (HR 0.06, 95% CI 0.03-0.12). Overall survival follow-up is ongoing; the number of events for a protocol-specified analysis has not been met. The safety profile was consistent with the 5-year results. With lorlatinib, treatment-related adverse events did not lead to discontinuations after the first 26 months. More genetic alterations were detected in circulating tumor DNA samples from early progressors than in long-term responders on lorlatinib; new potential resistance mechanisms were identified. CONCLUSIONS: With median PFS yet to be reached after 7 years of follow-up in CROWN, lorlatinib continues to show unprecedented long-term benefit in patients with advanced ALK-positive NSCLC. Patients without progression within 24 months on lorlatinib have a low risk of progression or death at year 7 and may continue long-term treatment. Findings suggest that sustained long-term disease control with first-line lorlatinib may enable advanced ALK-positive NSCLC to evolve toward a chronic condition.
Source: Annals of Oncology
Institutions: Massachusetts General Hospital, Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center, Peter MacCallum Cancer Centre, Universitat Autònoma de Barcelona, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Tennessee Oncology, University Health Network, Princess Margaret Cancer Centre, National Cancer Center Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Southern Medical University, National University Cancer Institute, Singapore, Centre Hospitalier Universitaire de Toulouse, Seoul National University, Seoul National University Hospital, Pfizer (United States), Pfizer (France), Chinese University of Hong Kong, State Key Laboratory of Oncology in South China
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,080
Funders: Pfizer, Guardant Health
OpenAlex ID: W7162771098