title: Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.
abstract: OBJECTIVE
  The CLEOPATRA (Clinical Evaluation of Trastuzumab and Pertuzumab) study demonstrated superior progression-free survival (PFS) and overall survival when pertuzumab was added to trastuzumab and docetaxel. Paclitaxel given once per week is effective and less toxic than docetaxel. We performed a phase II study to evaluate the efficacy and safety of pertuzumab and trastuzumab with paclitaxel given once per week.
  
  
  METHODS
  Patients with metastatic human epidermal growth factor receptor 2-positive breast cancer with zero to one prior therapy were enrolled. Treatment consisted of paclitaxel 80 mg/m(2) once per week plus trastuzumab (8 mg/kg loading dose → 6 mg/kg) once every 3 weeks plus pertuzumab (840 mg loading dose → 420 mg) once every 3 weeks, all given intravenously. The primary end point was 6-month PFS assessed by Kaplan-Meier methods.
  
  
  RESULTS
  From January 2011 to December 2013, we enrolled 69 patients: 51 (74%) and 18 (26%) treated in first- and second-line metastatic settings, respectively. At a median follow-up of 21 months (range, 3 to 38 months), 6-month PFS was 86% (95% CI, 75% to 92%). The median PFS was 19.5 months (95% CI, 14 to 26 months) overall. PFS was 24.2 months (95% CI, 14 months to not reached [NR]) and 16.4 months (95% CI, 8.5 months to NR) for those without and with prior treatment, respectively. At 1 year, Kaplan-Meier PFS was 70% (95% CI, 56% to 79%) overall, 71% (95% CI, 55% to 82%) for those without prior therapy, and 66% (95% CI, 40% to 83%) for those with prior therapy. Treatment was well-tolerated; there was no febrile neutropenia or symptomatic left ventricular systolic dysfunction.
  
  
  CONCLUSIONS
  Paclitaxel given once per week with trastuzumab and pertuzumab is highly active and well tolerated and seems to be an effective alternative to docetaxel-based combination therapy.
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY. dangc@mskcc.org.
authors.forename: Chau
authors.initials: C
authors.lastname: Dang
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Neil
authors.initials: N
authors.lastname: Iyengar
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Farrah
authors.initials: F
authors.lastname: Datko
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Andrea
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Maria
authors.initials: M
authors.lastname: Theodoulou
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Maura
authors.initials: M
authors.lastname: Dickler
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Shari
authors.initials: S
authors.lastname: Goldfarb
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Diana
authors.initials: D
authors.lastname: Lake
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Julie
authors.initials: J
authors.lastname: Fasano
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Monica
authors.initials: M
authors.lastname: Fornier
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Theresa
authors.initials: T
authors.lastname: Gilewski
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Shanu
authors.initials: S
authors.lastname: Modi
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Devika
authors.initials: D
authors.lastname: Gajria
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Moynahan
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Nicola
authors.initials: N
authors.lastname: Hamilton
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Maxine
authors.initials: M
authors.lastname: Jochelson
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab