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RESEARCH PRODUCT

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

Martin SebastianDietrich HadlerMaciej KrzakowskiRobert A. BeckmanJoachim Von PawelEwa ChmielowskaJon GreenbergQiang WangTara FoxMartin Reck

subject

MalePulmonary and Respiratory MedicineCancer Researchmedicine.medical_specialtyLung NeoplasmsNeutropeniaPaclitaxelmedicine.medical_treatmentPhases of clinical researchNeutropeniaAntibodies Monoclonal HumanizedPlaceboGastroenterologyDisease-Free SurvivalCarboplatinPlaceboschemistry.chemical_compoundDouble-Blind MethodCarcinoma Non-Small-Cell LungInternal medicineAntineoplastic Combined Chemotherapy ProtocolsmedicineHumansNeoplasm MetastasisTigatuzumabLung cancerNeoplasm StagingChemotherapybusiness.industryMiddle Agedmedicine.diseaseCarboplatinSurgeryEuropeReceptors TNF-Related Apoptosis-Inducing LigandOncologychemistryPaclitaxelFemalebusiness

description

Abstract 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.

yearjournalcountryeditionlanguage
2013-07-23Lung Cancer
https://doi.org/10.1016/j.lungcan.2013.09.014