title: Phase II, multicenter, open-label, randomized study of YM155 plus docetaxel as first-line treatment in patients with HER2-negative metastatic breast cancer.
abstract: The objective of this study was to assess the efficacy and tolerability of YM155, a survivin suppressor, in combination with docetaxel, compared with docetaxel alone in patients with HER2-negative metastatic breast cancer. This phase II, multicenter, open-label, 2-arm study randomized patients (≥18 years) with histologically or cytologically confirmed stage IV HER2-negative metastatic breast cancer and ≥1 measurable lesion, to receive docetaxel alone or docetaxel plus YM155. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), time to response (TTR), biomarker assessment, and analysis of circulating tumor cells. Patients were women diagnosed with HER2-negative breast cancer; most had received prior drug therapies. The median PFS was 8.4 months with YM155 plus docetaxel (n = 50) and 10.5 months with docetaxel alone (n = 51; HR 1.53; 95 % CI 0.83, 2.83; P = 0.176). No statistically significant differences were observed for secondary endpoints, although slightly greater OS (630 vs 601 days; P = 0.768), CBR (84.3 vs 82.0 %; P = 0.855), DOR, and TTR were observed with docetaxel alone compared with YM155 plus docetaxel, whereas ORR was similar (25.5 vs 26.0). The most common TEAEs observed with YM155 plus docetaxel compared with docetaxel alone were neutropenia (83.3 vs 84.3 %), alopecia (62.5 vs 52.9 %), fatigue (50 vs 41.2 %), and nausea (37.5 vs 41.2 %). Although YM155 is a novel drug that suppresses survivin, YM155 plus docetaxel exhibited no statistically significant differences in endpoints compared with docetaxel alone. The combination regimen was well tolerated.
authors.affiliation: Innere Medizin I, Klinikum Mutterhaus de Borromaerinnen GmbH, Trier, Germany, Clemens@mutterhaus.de.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Clemens
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Gladkov
authors.forename: Elaina
authors.initials: E
authors.lastname: Gartner
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vladimirov
authors.forename: John
authors.initials: J
authors.lastname: Crown
authors.forename: Joyce
authors.initials: J
authors.lastname: Steinberg
authors.forename: Fei
authors.initials: F
authors.lastname: Jie
authors.forename: Anne
authors.initials: A
authors.lastname: Keating
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D000077143:Docetaxel; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009285:Naphthoquinones / Q000008:administration & dosage* / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000077143:Docetaxel; D007093:Imidazoles; D009285:Naphthoquinones; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C523798:sepantronium