Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 (Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer
| Autor: | Sandra J. Meech, Emilio Bajetta, David Robert John Readett, Gary Middleton, Oscar Arrieta, Joan H. Schiller, Vera Hirsh, Aleksandra Szczesna, Mansoor N. Saleh, Michael Boyer, Roy T. Webb, Wilfried Eberhardt, Rebecca J. Benner, Luis Paz-Ares, Johannes Raats, Rafael Rosell, Camilla Fowst, Pavel Reiterer |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Agonist
Adult Male Cancer Research Pathology medicine.medical_specialty Lung Neoplasms Paclitaxel medicine.drug_class medicine.medical_treatment Medizin Carboplatin chemistry.chemical_compound Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols medicine Carcinoma Humans Lung cancer Receptor Aged Aged 80 and over Chemotherapy business.industry Cancer Middle Aged medicine.disease Treatment Outcome Oncology chemistry Oligodeoxyribonucleotides Toll-Like Receptor 9 Cancer research Disease Progression Female business |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 29(19) |
| ISSN: | 1527-7755 |
| Popis: | Purpose This phase III study examined efficacy of the synthetic Toll-like receptor 9–activating oligodeoxynucleotide PF-3512676 in combination with standard paclitaxel/carboplatin chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomly assigned (1:1) to receive up to six courses of paclitaxel/carboplatin (intravenous paclitaxel 200 mg/m2 and carboplatin at area under the [concentration-time] curve 6 on day 1 of a 3-week cycle) alone (control arm) or in combination with 0.2 mg/kg subcutaneous PF-3512676 on days 8 and 15 (investigational arm). Primary end point was overall survival (OS). Results Baseline demographics were similar across arms (N = 828). Most patients (88%) had stage IV disease. Median OS and median progression-free survival (PFS) were similar (OS: investigational arm, 10.0 months v control arm, 9.8 months; P = .56; PFS: investigational arm, 4.8 months v control arm, 4.7 months; P = .79). Most commonly reported PF-3512676–related adverse events (AEs) were mild-to-moderate local injection site reactions, pyrexia, and flu-like symptoms. In the investigational arm, grades 3 to 4 AEs, including neutropenia, thrombocytopenia, and anemia, were more frequent, and more patients had one or more sepsis-related AEs versus controls (17 v 3). At first interim analysis, the Data Safety Monitoring Committee recommended study discontinuation because of lack of incremental efficacy and more sepsis-related serious AEs in the PF-3512676 arm. Administration of PF-3512676, but not chemotherapy, was halted. Conclusion Addition of PF-3512676 to paclitaxel/carboplatin did not improve OS or PFS versus paclitaxel/carboplatin alone for first-line treatment of patients with advanced NSCLC but did increase toxicity. This regimen cannot be recommended for treating patients with advanced NSCLC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|