title: Oral vinorelbine in combination with trastuzumab as a first-line therapy of metastatic or locally advanced HER2-positive breast cancer.
abstract: Vinorelbine-trastuzumab combination proved to be an effective first-line treatment for patients with locally advanced or metastatic breast cancer (MBC). Oral chemotherapy represents a step forward in MBC management. To improve patients' comfort using the oral form of vinorelbine, we conducted a multicenter phase II study to investigate the efficacy and safety of the oral vinorelbine-trastuzumab combination in women with MBC with human epidermal growth factor receptor 2 (HER2) overexpression.
  
  
  
  Main eligibility criteria: HER2-positive disease, no adjuvant chemotherapy within the last 6 months and no prior chemotherapy for MBC. Patients were treated with oral vinorelbine 80 mg/m(2) D1, D8, D15 (following first 3 administrations at 60 mg/m(2) during the first cycle) for a total of 8 cycles (1 cycle = 3 weeks), in combination with trastuzumab 6 mg/kg on D1 (loading dose: 8 mg/kg) every 3 weeks or 4 mg/kg (loading dose: 6 mg/kg) weekly. Response was evaluated every 2 cycles using RECIST 1.0.
  
  
  
  objective response rate (ORR); secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
  
  
  
  In the full population (n = 26), median age was 50.7 years and median WHO PS 0. Median disease-free interval was 50.7 months [95 % CI (43.6-57.9)]. In the evaluable patients population, ORR was 56 % [95 % CI (34.9-75.6)], including 3 complete responses (12 %) and 11 partial (44 %); 8 (32 %) patients had stable disease resulting in a clinical benefit (or disease control) rate of 88 % [95 % CI (68.8-97.5)]. Median DOR was 7.1 months [95 % CI (3.9-10.2)], median PFS 6.7 months (95 % CI 3.5-10), and median OS 27.9 months (95 % CI 17.4-38.3). Treatment was generally well tolerated with main observed grade 3/4 hematological toxicities being neutropenia (46 %) and anemia (4 %). Grade 3-4 nausea-vomiting were observed in 11.5 % of patients.
  
  
  
  Our results confirm the efficacy of oral vinorelbine-trastuzumab combination as a first-line treatment in HER2-positive locally advanced or MBC patients with an acceptable safety profile. Oral vinorelbine-trastuzumab optimizes the convenience of this chemotherapy regimen, especially for patients receiving trastuzumab every 3 weeks.
authors.affiliation: Department of Hematology-Oncology, Hammoud Hospital University Medical Centre, 652 G. Hammoud Street, Sidon, Lebanon. drfadi.research@gmail.com.|Faculty of Medicine, Lebanese University, Beirut, Lebanon. drfadi.research@gmail.com.|Faculty of Medicine, Saint Joseph University, Beirut, Lebanon. drfadi.research@gmail.com.
authors.forename: Fadi
authors.initials: F
authors.lastname: Farhat
authors.affiliation: Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.|Department of Hematology-Oncology, Hôtel-Dieu de France University Hospital, Beirut, Lebanon.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Kattan
authors.affiliation: Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.|Department of Hematology-Oncology, Hôtel-Dieu de France University Hospital, Beirut, Lebanon.
authors.forename: Marwan
authors.initials: M
authors.lastname: Ghosn
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D066066:Response Evaluation Criteria in Solid Tumors; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D014747:Vinblastine; D000077235:Vinorelbine; C508053:ERBB2 protein, human
keywords: Efficacy; First-line therapy; HER2-positive; Metastatic breast cancer; Oral chemotherapy; Safety