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
14 affiliations
- 1Department of Medical Oncology, Dana-Farber Cancer Institute and Massachusetts General Hospital Cancer Center, Boston, USA. Electronic address: [email protected]
- 2Department of Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
- 3Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain
- 4Tennessee Oncology, PLLC, Greco-Hainsworth Centers for Research, Nashville, USA
- 5Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
- 6Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan
- 7Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, China
- 8Department of Haematology-Oncology, National University Cancer Institute, Singapore
- 9Thoracic Oncology Department, Toulouse University Hospital, Toulouse, France
- 10Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea
- 11Translational Oncology, Pfizer, La Jolla, USA
- 12Oncology Drug Development, Pfizer, Milan, Italy
- 13Oncology Lung Cancer, Pfizer, Paris, France
- 14Department of Clinical Oncology, State Key Laboratory of South China, Chinese University of Hong Kong, Hong Kong Special Administrative Region of China, China
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.
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BibTeX
@article{shaw2026lorlatinib,
title = {{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}},
author = {Alice Tsang Shaw and Benjamin Solomon and Enriqueta Felip and Todd Michael Bauer and G. Liu and Y. Goto and Yan Wu and R.A. Soo and Julien Mazières and D G Kim and I.‐M. Wang and Jolanda Paolini and Anna Polli and N. Rifi and Francesca Toffalorio and T.S.K. Mok},
journal = {Annals of Oncology},
year = {2026},
month = may,
doi = {10.1016/j.annonc.2026.05.692},
url = {https://doi.org/10.1016/j.annonc.2026.05.692},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 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
AU - Alice Tsang Shaw
AU - Benjamin Solomon
AU - Enriqueta Felip
AU - Todd Michael Bauer
AU - G. Liu
AU - Y. Goto
AU - Yan Wu
AU - R.A. Soo
AU - Julien Mazières
AU - D G Kim
AU - I.‐M. Wang
AU - Jolanda Paolini
AU - Anna Polli
AU - N. Rifi
AU - Francesca Toffalorio
AU - T.S.K. Mok
PY - 2026
DA - 2026/05/29
JO - Annals of Oncology
DO - 10.1016/j.annonc.2026.05.692
UR - https://doi.org/10.1016/j.annonc.2026.05.692
AB - 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.
SN - 0923-7534
SN - 1569-8041
ER -