title: Randomized phase II trial of first-line trastuzumab plus docetaxel and capecitabine compared with trastuzumab plus docetaxel in HER2-positive metastatic breast cancer.
abstract: PURPOSE To evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer. PATIENTS AND METHODS Patients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m(2) in HTX arm, 100 mg/m(2) in HT arm, every 3 weeks) with or without X (950 mg/m(2) twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR). Results In 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm. CONCLUSION HTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.
authors.affiliation: Cancer Research UK Department of Medical Oncology, The Christie, 550 Wilmslow Rd, Manchester, M20 4BX, United Kingdom. andrew.wardley@christie.nhs.uk
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wardley
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
authors.forename: Flavia
authors.initials: F
authors.lastname: Morales-Vasquez
authors.forename: Luis M
authors.initials: LM
authors.lastname: Zetina
authors.forename: Maria
authors.initials: M
authors.lastname: de Fátima Dias Gaui
authors.forename: Douglas Otero
authors.initials: DO
authors.lastname: Reyes
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Claire
authors.initials: C
authors.lastname: Barton
authors.forename: Peter
authors.initials: P
authors.lastname: Button
authors.forename: Veronica
authors.initials: V
authors.lastname: Hersberger
authors.forename: Antonio Antón
authors.initials: AA
authors.lastname: Torres
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007390:International Agencies; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D003841:Deoxycytidine; D000077143:Docetaxel; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab