First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study.


Autoria(s): Douillard, J-Y; Ostoros, G; Cobo, M; Ciuleanu, T; McCormack, R; Webster, A; Milenkova, T
Data(s)

11/06/2014

11/06/2014

07/01/2014

Resumo

BACKGROUND Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). METHODS Treatment: gefitinib 250 mg day(-1) until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. RESULTS Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8%; adenocarcinoma 97.2%; never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5-77.7), DCR 90.6% (95% CI 83.5-94.8), median PFS 9.7 months (95% CI 8.5-11.0), median OS 19.2 months (95% CI 17.0-NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15%; SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8-74.7). CONCLUSION First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.

Clinical Trial, Phase IV; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't;

This study was funded by AstraZeneca

Identificador

Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br. J. Cancer. 2014; 110(1):55-62

1532-1827 (Online)

0007-0920 (Print)

PMC3887309

http://hdl.handle.net/10668/1633

24263064

10.1038/bjc.2013.721

Idioma(s)

en

Publicador

Cancer Research UK

Relação

British Journal of Cancer

http://www.nature.com/bjc/journal/v110/n1/full/bjc2013721a.html#abs

Direitos

Acceso abierto

Palavras-Chave #Gefitinib #NSCLC #EGFR mutation #Caucasian #Carcinoma de pulmón de células no pequeñas #Mutación #Estudios prospectivos #Inhibidores de proteína cinasas #Quinazolinas #Receptor del factor de crecimiento epidérmico #Antineoplásicos #Grupo de ascendencia continental europea #Genes erbB-1 #Neoplasias pulmonares #Medical Subject Headings::Named Groups::Persons::Age Groups::Adult #Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged #Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents #Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung #Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Disease-Free Survival #Medical Subject Headings::Named Groups::Persons::Population Groups::Continental Population Groups::European Continental Ancestry Group #Medical Subject Headings::Check Tags::Female #Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Neoplasm::Oncogenes::Proto-Oncogenes::Genes, erbB::Genes, erbB-1 #Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans #Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms #Medical Subject Headings::Check Tags::Male #Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Aged #Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies #Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors #Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Quinazolines #Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptor Protein-Tyrosine Kinases::Receptor, Epidermal Growth Factor #Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Young Adult #Medical Subject Headings::Named Groups::Persons::Age Groups::Adolescent
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/published

Artículo