A randomized, double-blind, placebo-controlled phase 2 study of tigatuzumab (CS-1008) in combination with carboplatin/paclitaxel in patients with chemotherapy-naïve metastatic/unresectable non-small cell lung cancer
| Autor: | Martin Sebastian, Dietrich Hadler, Maciej Krzakowski, Robert A. Beckman, Joachim von Pawel, Ewa Chmielowska, Jon Greenberg, Qiang Wang, Tara Fox, Martin Reck |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Cancer Research medicine.medical_specialty Lung Neoplasms Neutropenia Paclitaxel medicine.medical_treatment Phases of clinical research Antibodies Monoclonal Humanized Placebo Gastroenterology Disease-Free Survival Carboplatin Placebos chemistry.chemical_compound Double-Blind Method Carcinoma Non-Small-Cell Lung Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Neoplasm Metastasis Tigatuzumab Lung cancer Neoplasm Staging Chemotherapy business.industry Middle Aged medicine.disease Surgery Europe Receptors TNF-Related Apoptosis-Inducing Ligand Oncology chemistry Female business |
| Zdroj: | Lung Cancer. 82:441-448 |
| ISSN: | 0169-5002 |
| DOI: | 10.1016/j.lungcan.2013.09.014 |
| Popis: | Introduction Tigatuzumab, a humanized monoclonal DR5 agonist antibody induces apoptosis in human cancer cell lines. The objective of this study was to investigate the antitumor effects of tigatuzumab combined with carboplatin/paclitaxel in chemotherapy-naive patients with metastatic/unresectable non-small cell lung cancer (NSCLC). Methods Patients with histologically or cytologically confirmed NSCLC stage IIIB/IV disease by RECIST (version 1.0) and ECOG-PS 0–1 were enrolled at 15 European sites. Patients received tigatuzumab or placebo intravenously with carboplatin/paclitaxel every 3 weeks (1 cycle) for up to 6 cycles. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate and safety. Results 97 patients were analyzed for efficacy (49 tigatuzumab; 48 placebo). Median PFS (95% CI) was 5.4 months (3.3, 6.6) for tigatuzumab compared with 4.3 months (4.1, 5.8) for placebo. Median OS (95% CI) was 8.4 months (6.9, 16.3) for tigatuzumab versus 9.0 months (7.6, 14.5) for placebo. 12 patients (24.5%) in the tigatuzumab arm and 11 patients (22.9%) in the placebo arm had partial response. No patient had complete response. In a prospectively-defined Fc gamma receptor genotype subset ( n =25), there was a non-significant trend toward increased PFS with tigatuzumab versus placebo (HR=0.47; 95% CI: 0.16, 1.35) but no difference in OS. Tigatuzumab was well tolerated. However, grade 3/4 neutropenia was reported in 10 patients (20.4%) receiving tigatuzumab compared with 4 patients (8.3%) receiving placebo. Conclusions Tigatuzumab was well tolerated but did not improve efficacy of carboplatin/paclitaxel in systemic therapy-naive, unselected advanced NSCLC patients. Clinical trials identifier: NCT00991796. |
| Databáze: | OpenAIRE |
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