Brigatinib Versus Crizotinib in ALK Inhibitor–Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial
| Autor: | D. Ross Camidge, Myung-Ju Ahn, Maximilian Hochmair, Ji Youn Han, Enriqueta Felip, Marcello Tiseo, Dong Wan Kim, Sanjay Popat, Raffaele Califano, Huifeng Niu, Pingkuan Zhang, Alexander I. Spira, Ki Hyeong Lee, Florin Vranceanu, Hye Ryun Kim, Yuyin Liu, James Chih-Hsin Yang, Angelo Delmonte, Frank Griesinger, Scott N. Gettinger, Maria Rosario Garcia Campelo, Huamao M. Lin |
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| Přispěvatelé: | Institut Català de la Salut, [Camidge DR] Department of Medicine, University of Colorado Cancer Center, Aurora, Colorado. [Kim HR] Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. [Ahn MJ] Division of Hematology-Oncology, Samsung Medical Center, Seoul, South Korea. [Yang JCH] Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan. [Han JY] Department of Precision Medicine, National Cancer Center, Gyeonggi, South Korea. [Hochmair MJ] Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Vienna, Austria. [Felip E] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
Oncology medicine.medical_specialty Lung Neoplasms medicine.drug_class Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] Phases of clinical research Other subheadings::Other subheadings::/drug therapy [Other subheadings] Organophosphorus Compounds Crizotinib Internal medicine medicine Clinical endpoint Humans Anaplastic lymphoma kinase Anaplastic Lymphoma Kinase Lung cancer Protein Kinase Inhibitors business.industry Hazard ratio Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma Bronchogenic::Carcinoma Non-Small-Cell Lung [DISEASES] neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES] medicine.disease ALK inhibitor Pyrimidines Tolerability Avaluació de resultats (Assistència sanitària) business Pulmons - Càncer - Tractament medicine.drug |
| Zdroj: | Scientia |
| ISSN: | 1556-0864 |
| Popis: | ALK tyrosine kinase inhibitor; Brigatinib; Non–small cell lung cancer Inhibidor de la tirosina quinasa ALK; Brigatinib; Cáncer de pulmón de células no pequeñas Inhibidor de la tirosina cinasa ALK; Brigatinib; Càncer de pulmó de cèl·lules no petites Introduction In the phase 3 study entitled ALK in Lung cancer Trial of brigAtinib in 1st Line (ALTA-1L), which is a study of brigatinib in ALK inhibitor–naive advanced ALK-positive NSCLC, brigatinib exhibited superior progression-free survival (PFS) versus crizotinib in the two planned interim analyses. Here, we report the final efficacy, safety, and exploratory results. Methods Patients were randomized to brigatinib 180 mg once daily (7-d lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was a blinded independent review committee–assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy. Results A total of 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up = 40.4 mo), the 3-year PFS by blinded independent review committee was 43% (brigatinib) versus 19% (crizotinib; median = 24.0 versus 11.1 mo, hazard ratio [HR] = 0.48, 95% confidence interval [CI]: 0.35–0.66). The median overall survival was not reached in either group (HR = 0.81, 95% CI: 0.53–1.22). Posthoc analyses suggested an overall survival benefit for brigatinib in patients with baseline brain metastases (HR = 0.43, 95% CI: 0.21–0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib exhibited superior efficacy compared with crizotinib regardless of EML4-ALK variant and TP53 mutation. Emerging secondary ALK mutations were rare in patients progressing on brigatinib. No new safety signals were observed. Conclusions In the ALTA-1L final analysis, with longer follow-up, brigatinib continued to exhibit superior efficacy and tolerability versus crizotinib in patients with or without poor prognostic biomarkers. The suggested survival benefit with brigatinib in patients with brain metastases warrants future study. |
| Databáze: | OpenAIRE |
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