Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non-small-cell lung cancer
Autor: | Wolfram Brugger, David E. Gerber, Dora Ferrari, Susan T Arthur, Joan H. Schiller, Edward Graeme Garmey, Yinpu Chen, Brian Schwartz, Sergey Orlov, Wallace Akerley, Igor Gorbachevsky, Rodryg Ramlau, Lecia V. Sequist, Joachim von Pawel, Daniel B. Costa |
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Rok vydání: | 2011 |
Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty Lung Neoplasms medicine.drug_class Pharmacology medicine.disease_cause Tyrosine-kinase inhibitor Disease-Free Survival c-Met inhibitor Placebos chemistry.chemical_compound Erlotinib Hydrochloride Internal medicine Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols Medicine Humans Receptors Growth Factor Epidermal growth factor receptor Tivantinib Neoplasm Metastasis Lung cancer Aged Aged 80 and over biology business.industry Middle Aged Proto-Oncogene Proteins c-met medicine.disease Survival Analysis Pyrrolidinones respiratory tract diseases chemistry biology.protein Quinazolines Quinolines Female Erlotinib KRAS business medicine.drug |
Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 29(24) |
ISSN: | 1527-7755 |
Popis: | Purpose c-MET (MET) receptor activation is associated with poor prognosis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non–small-cell lung cancer (NSCLC). This global, randomized phase II trial examined erlotinib plus tivantinib (ARQ 197; ArQule, Woburn, MA), a novel MET inhibitor. Methods Previously treated patients with EGFR TKI–naive advanced NSCLC were randomly assigned to receive oral erlotinib (150 mg daily) plus oral tivantinib (360 mg twice daily) or erlotinib plus placebo (EP). The primary end point was progression-free survival (PFS). At the time of progression, cross-over from EP to erlotinib plus tivantinib (ET) was permitted. Archival tumor tissue specimens were required. Results One hundred sixty-seven patients were randomly assigned to ET (n = 84) and to EP (n = 83). Median PFS was 3.8 months for ET and 2.3 months for EP (hazard ratio [HR], 0.81; 95% CI, 0.57 to 1.16; P = .24). Exploratory analysis revealed that the small cohort with KRAS mutations achieved a PFS HR of 0.18 (95% CI, 0.05 to 0.70; interaction P = .006). Objective responses were seen in 10% of patients on ET, 7% of patients on EP, and in two patients who crossed over from EP to ET, including one with EGFR mutation and MET gene copy number greater than 5. There were no significant differences in adverse events between study arms. Conclusion The combination of the MET inhibitor tivantinib and erlotinib is well-tolerated. Although the study did not meet its primary end point, evidence of activity was demonstrated, especially among patients with KRAS mutations. Additional study of tivantinib and erlotinib in patients with NSCLC is planned. |
Databáze: | OpenAIRE |
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