title: A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer.
abstract: We aimed to evaluate the efficacy and feasibility of combining trastuzumab/vinorelbine with bevacizumab in patients with first-or second-line HER2-positive, metastatic breast cancer (MBC). Eligible patients had HER2-positive measureable MBC, with no more than one prior line of chemotherapy, and were treated with trastuzumab (4 mg/kg × 2 mg/kg weekly thereafter), vinorelbine (25 mg/m(2) weekly), and bevacizumab (10 mg/kg every 2 weeks). Co-primary endpoints were (a) the proportion of patients alive and progression-free at 1 year and (b) safety profile/feasibility. Feasibility was defined as a rate of grade 3/4 non-hematologic toxicity attributable to protocol-based therapy <20 %. Twenty-nine patients were enrolled (n = 22 first-line, n = 7 second-line). Median age was 48 years (range 37-68). The median number of cycles received was 8 (1-23) and median duration on treatment was 7.4 months (range 1-22). The study was closed early due to higher-than-expected rates of grade 3/4 non-hematologic toxicities, with 50 events in 20 patients. A total of six patients (21 %) were taken off study for treatment-related toxicity. Most common treatment-related toxicities included fatigue (n = 7), febrile neutropenia (n = 4), and headache (n = 3). At 1 year, 8/22 first-line (36 %) and 2/7 second-line (29 %) patients were alive and progression-free. Median PFS was 9.9 months and 7.8 months in the first- and second-line cohorts, respectively. Objective responses were observed in 16/22 (73 %) and 5/7 (71 %) patients in the first- and second-line settings. Although the combination of vinorelbine, trastuzumab, and bevacizumab showed notable activity in HER2-positive MBC, the proportion of first-line patients alive and progression-free at 1 year was deemed unlikely to reach the pre-defined threshold for declaring success. Additionally, unacceptable toxicity was observed, at rates greater than previously reported with vinorelbine/trastuzumab or vinorelbine/bevacizumab doublet combinations.
authors: Department of Medical Oncology, Division of Women's Cancers, Dana-Farber Cancer Institute, Boston, MA 02115, USA. nlin@partners.org
authors: N U
authors: NU
authors: Lin
authors: D S
authors: DS
authors: Seah
authors: R
authors: R
authors: Gelman
authors: S
authors: S
authors: Desantis
authors: E L
authors: EL
authors: Mayer
authors: S
authors: S
authors: Isakoff
authors: P
authors: P
authors: Dipiro
authors: I E
authors: IE
authors: Krop
authors: S E
authors: SE
authors: Come
authors: D
authors: D
authors: Weckstein
authors: E P
authors: EP
authors: Winer
authors: H J
authors: HJ
authors: Burstein
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D014747:Vinblastine; D000077235:Vinorelbine