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A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer
- Source :
- Annals of Oncology. 26:354-362
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Imetelstat, a novel telomerase inhibitor, failed to improve significantly median PFS and OS as maintenance therapy (±bevacizumab) in advanced NSCLC. Telomere length (TL) biomarker results were consistent with the hypothesis that telomerase inhibition is of greater benefit to patients with tumors possessing shorter telomeres; the patients with shorter TL had a trend toward longer median PFS and OS. Background Continuation or ‘switch’ maintenance therapy is commonly used in patients with advancd non-small-cell lung cancer (NSCLC). Here, we evaluated the efficacy of the telomerase inhibitor, imetelstat, as switch maintenance therapy in patients with advanced NSCLC. Patients and methods The primary end point of this open-label, randomized phase II study was progression-free survival (PFS). Patients with non-progressive, advanced NSCLC after platinum-based doublet (first-line) chemotherapy (with or without bevacizumab), any histology, with Eastern Cooperative Oncology Group performance status 0–1 were eligible. Randomization was 2 : 1 in favor of imetelstat, administered at 9.4 mg/kg on days 1 and 8 of a 21-day cycle, or observation. Telomere length (TL) biomarker exploratory analysis was carried out in tumor tissue by quantitative PCR (qPCR) and telomerase fluorescence in situ hybridization. Results Of 116 patients enrolled, 114 were evaluable. Grade 3/4 neutropenia and thrombocytopenia were more frequent with imetelstat. Median PFS was 2.8 and 2.6 months for imetelstat-treated versus control [hazard ratio (HR) = 0.844; 95% CI 0.54–1.31; P = 0.446]. Median survival time favored imetelstat (14.3 versus 11.5 months), although not significantly (HR = 0.68; 95% CI 0.41–1.12; P = 0.129). Exploratory analysis demonstrated a trend toward longer median PFS (HR = 0.43; 95% CI 0.14–1.3; P = 0.124) and overall survival (OS; HR = 0.41; 95% CI 0.11–1.46; P = 0.155) in imetelstat-treated patients with short TL, but no improvement in median PFS and OS in patients with long TL (HR = 0.86; 95% CI 0.39–1.88; and HR = 0.51; 95% CI 0.2–1.28; P = 0.145). Conclusions Maintenance imetelstat failed to improve PFS in advanced NSCLC patients responding to first-line therapy. There was a trend toward a improvement in median PFS and OS in patients with short TL. Short TL as a predictive biomarker will require further investigation for the clinical development of imetelstat.
- Subjects :
- Adult
Male
Niacinamide
Oncology
Telomerase
medicine.medical_specialty
Indoles
Lung Neoplasms
Bevacizumab
Oligonucleotides
Phases of clinical research
Antineoplastic Agents
Kaplan-Meier Estimate
Neutropenia
Disease-Free Survival
Maintenance Chemotherapy
Imetelstat
Maintenance therapy
Carcinoma, Non-Small-Cell Lung
Internal medicine
medicine
Humans
Enzyme Inhibitors
Lung cancer
neoplasms
In Situ Hybridization, Fluorescence
Aged
Proportional Hazards Models
Aged, 80 and over
business.industry
Hazard ratio
Original Articles
Hematology
Middle Aged
Telomere
medicine.disease
Surgery
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 09237534
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Annals of Oncology
- Accession number :
- edsair.doi.dedup.....a76622af4d486d892be15b322f2a1979