A randomized phase II trial of mapatumumab, a TRAIL-R1 agonist monoclonal antibody, in combination with carboplatin and paclitaxel in patients with advanced NSCLC
| Autor: | Gilles Gallant, D. R. Camidge, C. L. Cebotaru, N. L. Fox, E Kumm, J. von Pawel, Martin Reck, David R. Spigel, Mircea Dediu, J. H. Harvey |
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| Rok vydání: | 2010 |
| Předmět: |
Agonist
Oncology Cancer Research medicine.medical_specialty medicine.drug_class business.industry Pharmacology medicine.disease Monoclonal antibody Carboplatin chemistry.chemical_compound Paclitaxel chemistry Internal medicine Toxicity medicine In patient Lung cancer business Mapatumumab medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 28:LBA7501-LBA7501 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2010.28.18_suppl.lba7501 |
| Popis: | LBA7501 Background: Mapatumumab, a fully human agonist monoclonal antibody, targets and activates the death receptor TRAIL-R1. We conducted this randomized, controlled phase II trial to evaluate mapatumumab in combination with carboplatin and paclitaxel as first-line therapy in advanced non-small call lung cancer (NSCLC). Methods: Patients were required to have histologically or cytologically confirmed Stage IIIB or IV advanced primary NSCLC with measurable disease by RECIST. Patients were randomly assigned to Arm A, paclitaxel 200 mg/m2 + carboplatin AUC 6.0 (PC); Arm B, PC + mapatumumab 10 mg/kg; or Arm C, PC + mapatumumab 30 mg/kg. Cycles were repeated every 21 days; patients completed up to 6 cycles in the absence of evidence of disease progression or unacceptable toxicity. Patients in Arms B and C could receive additional cycles of mapatumumab in the absence of disease progression. The co-primary endpoints were response rate (RR; complete response + partial response) and progression-free survival (PFS). Images were read by independent radiologists blinded to treatment group assignment, as well as locally. Results: 111 patients were enrolled at 22 sites in 4 countries. Addition of mapatumumab to PC did not improve RR or PFS. RR and PFS, based on the independent read, and overall survival results are summarized below. The results based on local reading also showed no benefit from the addition of mapatumumab to PC. Adverse events were generally balanced across treatment groups; there was no evidence that mapatumumab exacerbated toxicities associated with PC. Conclusions: The results do not support further evaluation of mapatumumab in combination with PC in patients with advanced NSCLC. Additional trials of mapatumumab in other indications are ongoing. [Table: see text] [Table: see text] |
| Databáze: | OpenAIRE |
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