1. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer
- Author
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Shaw, A. T., Bauer, T. M., De Marinis, F., Felip, E., Goto, Y., Liu, G., Mazieres, J., Kim, D. -W., Mok, T., Polli, A., Thurm, H., Calella, A. M., Peltz, G., Solomon, B. J., and Soto Parra, H.
- Subjects
Male ,Alectinib ,Lung Neoplasms ,Carcinoma, Non-Small-Cell Lung/drug therapy ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Macrocyclic ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,hemic and lymphatic diseases ,Anaplastic lymphoma kinase ,Anaplastic Lymphoma Kinase ,030212 general & internal medicine ,Non-Small-Cell Lung ,Manchester Cancer Research Centre ,General Medicine ,Middle Aged ,Crizotinib/adverse effects ,Intention to Treat Analysis ,Female ,Hyperlipidemias/chemically induced ,medicine.drug ,Adult ,Lactams, Macrocyclic/adverse effects ,Lactams ,Lactams, Macrocyclic ,Anaplastic Lymphoma Kinase/antagonists & inhibitors ,Antineoplastic Agents ,Hyperlipidemias ,03 medical and health sciences ,Crizotinib ,ROS1 ,medicine ,Humans ,Lung Neoplasms/drug therapy ,Lung cancer ,Aged ,Chemotherapy ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Carcinoma ,Cancer ,Antineoplastic Agents/adverse effects ,medicine.disease ,Survival Analysis ,Lorlatinib ,Mutation ,Cancer research ,business - Abstract
BACKGROUND: Lorlatinib, a third-generation inhibitor of anaplastic lymphoma kinase (ALK), has antitumor activity in previously treated patients with ALK-positive non-small-cell lung cancer (NSCLC). The efficacy of lorlatinib, as compared with that of crizotinib, as first-line treatment for advanced ALK-positive NSCLC is unclear. METHODS: We conducted a global, randomized, phase 3 trial comparing lorlatinib with crizotinib in 296 patients with advanced ALK-positive NSCLC who had received no previous systemic treatment for metastatic disease. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included independently assessed objective response and intracranial response. An interim analysis of efficacy was planned after approximately 133 of 177 (75%) expected events of disease progression or death had occurred. RESULTS: The percentage of patients who were alive without disease progression at 12 months was 78% (95% confidence interval [CI], 70 to 84) in the lorlatinib group and 39% (95% CI, 30 to 48) in the crizotinib group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.19 to 0.41; PCONCLUSIONS: In an interim analysis of results among patients with previously untreated advanced ALK-positive NSCLC, those who received lorlatinib had significantly longer progression-free survival and a higher frequency of intracranial response than those who received crizotinib. The incidence of grade 3 or 4 adverse events was higher with lorlatinib than with crizotinib because of the frequent occurrence of altered lipid levels. (Funded by Pfizer; CROWN ClinicalTrials.gov number, NCT03052608.).
- Published
- 2020