A randomized phase II study of the telomerase inhibitor XXXX as maintenance therapy for advanced @entity1149 .

@entity1 @entity882 @entity5 @entity15154 @entity1149 @entity1398 @entity902 @entity1349
BACKGROUND: Continuation or 'switch' maintenance therapy is commonly used in @entity1 with @entity1149 ( @entity1149 ). Here, we evaluated the efficacy of the telomerase inhibitor, @entity15154 , as switch maintenance therapy in @entity1 with advanced @entity1149 . @entity1 AND METHODS: The primary end point of this open-label, randomized phase II study was progression-free survival (PFS). @entity1 with non-progressive, advanced @entity1149 after @entity902 -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 @entity15154 , 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 @entity5 tissue by quantitative PCR (qPCR) and telomerase fluorescence in situ hybridization. RESULTS: Of 116 @entity1 enrolled, 114 were evaluable. Grade 3/4 @entity1398 and @entity882 were more frequent with @entity15154 . Median PFS was 2.8 and 2.6 months for @entity15154 -treated versus control [hazard ratio (HR) = 0.844; 95% CI 0.54-1.31; P = 0.446]. Median survival time favored @entity15154 (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 @entity1349 ( @entity1349 ; HR = 0.41; 95% CI 0.11-1.46; P = 0.155) in @entity15154 -treated @entity1 with short TL, but no improvement in median PFS and @entity1349 in @entity1 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 @entity15154 failed to improve PFS in advanced @entity1149 @entity1 responding to first-line therapy. There was a trend toward a improvement in median PFS and @entity1349 in @entity1 with short TL. Short TL as a predictive biomarker will require further investigation for the clinical development of @entity15154 .
