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Ann Oncol. 2015 Feb;26(2):354-62. doi: 10.1093/annonc/mdu550. Epub 2014 Dec 2.

A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer.

Author information

1
Thoracic Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa alberto.chiappori@moffitt.org.
2
Department of Oncology, Kaiser Permanente Medical Center, Vallejo.
3
Research Consortium, Sarah Cannon Research Institute, Nashville.
4
Thoracic Department, Cancer Care Associates of Fresno Medical Group, Fresno.
5
Oncology Hematology Department, Kaiser Permanente Northwest, Portland.
6
Karmanos Cancer Institute, Detroit, USA.
7
CHUM-Hopital Notre-Dame, Montreal, Quebec, Canada.
8
Department of Oncology, Asklepios Fachkliniken Muenchen-Gauting, Gauting, Bayern, Germany.
9
Sarah Cannon Florida Cancer Specialists, Bonita Springs, USA.
10
Department of Thoracic Oncology, LungenClinic Grosshansdorf, member of the German Center for Lung Research (DZL), Grosshansdorf, Germany.
11
Department of Biostatistics, Geron Corporation, Menlo Park.
12
Department of Oncology, University of Texas Southwestern Medical Center, Dallas, USA.

Abstract

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.

KEYWORDS:

biomarker; imetelstat; non-small-cell lung cancer

PMID:
25467017
PMCID:
PMC4304381
DOI:
10.1093/annonc/mdu550
[Indexed for MEDLINE]
Free PMC Article

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