title: Phase III study on efficacy of taxanes plus bevacizumab with or without capecitabine as first-line chemotherapy in metastatic breast cancer.
abstract: Taxanes (T) plus bevacizumab (B) and taxanes plus capecitabine (X) showed better progression-free survival (PFS) compared to taxanes alone. Since life-threatening or highly symptomatic situations require polychemotherapy in metastatic breast cancer (MBC), combination of taxanes, capecitabine plus bevacizumab appears reasonable. TABEA (NCT01200212), a prospectively randomized, open-label, phase III trial compares taxanes (paclitaxel 80 mg/m(2) i.v. d1,8,15 q22 or docetaxel 75 mg/m(2) i.v. d1 q22) plus bevacizumab (15 mg/kg i.v. d1 q22) with (TBX) or without capecitabine (TB, 1800 mg/m(2) daily d1-14 q22) as first-line therapy in MBC. Histologically confirmed HER2-negative, locally advanced or MBC patients with a chemotherapy indication and measurable or non-measurable target lesions (RECIST criteria) were included. Primary objective was PFS. Secondary objectives were response rate and duration, clinical benefit rate (complete response, partial response, stable disease ≥24 weeks), 3-year overall survival, PFS in patients ≥65 years, toxicity, and compliance. We assumed 10 and 13.3 months PFS for TB and TBX, respectively (HR = 0.75), requiring 432 patients and 386 events. Preplanned interim futility and safety analyses after 100 events in 202 patients showed no efficacy benefit and higher toxicity for TBX. Recruitment and therapy were stopped following advice from the IDMC. Final analysis revealed a HR 1.13 [95 %CI 0.806-1.59], P = 0.474, for PFS. Overall grade 3-4 adverse event (77.3 vs. 62.1 %, P = 0.014) and serious adverse event (40.0 vs. 30.2 %, P = 0.127) rates were higher for TBX after 26.1 months median follow-up, with six deaths for TBX versus 1 for TB. Adding capecitabine to TB cannot be recommended as first-line therapy in MBC.
authors.affiliation: Gynecologic Oncology Practice Hannover, Hannover, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lück
authors.forename: Kristina
authors.initials: K
authors.lastname: Lübbe
authors.forename: Mattea
authors.initials: M
authors.lastname: Reinisch
authors.forename: Nicolai
authors.initials: N
authors.lastname: Maass
authors.forename: Gabriele
authors.initials: G
authors.lastname: Feisel-Schwickardi
authors.forename: Oliver
authors.initials: O
authors.lastname: Tomé
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.forename: Mustafa
authors.initials: M
authors.lastname: Aydogdu
authors.forename: Tanja
authors.initials: T
authors.lastname: Neunhöffer
authors.forename: Angelika
authors.initials: A
authors.lastname: Ober
authors.forename: Bahriye
authors.initials: B
authors.lastname: Aktas
authors.forename: Tjoung-Won
authors.initials: TW
authors.lastname: Park-Simon
authors.forename: Claudia
authors.initials: C
authors.lastname: Schumacher
authors.forename: Heinz-Gert
authors.initials: HG
authors.lastname: Höffkes
authors.forename: Thomas
authors.initials: T
authors.lastname: Illmer
authors.forename: Harald
authors.initials: H
authors.lastname: Wagner
authors.forename: Keyur
authors.initials: K
authors.lastname: Mehta
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Valentina
authors.initials: V
authors.lastname: Nekljudova
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D000077143:Docetaxel; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil