title: Safety profile of Pertuzumab with Trastuzumab and Docetaxel in patients from Asia with human epidermal growth factor receptor 2-positive metastatic breast cancer: results from the phase III trial CLEOPATRA.
abstract: BACKGROUND
  We report detailed safety analyses by geographic region from the phase III study CLEOPATRA with pertuzumab, trastuzumab, and docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive first-line metastatic breast cancer.
  
  
  METHODS
  Patients received pertuzumab/placebo at 840 mg in cycle 1 and 420 mg in subsequent cycles, and trastuzumab at 8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles; docetaxel was initiated at 75 mg/m(2). All study drugs were given intravenously, 3 times weekly.
  
  
  RESULTS
  Docetaxel dose reductions below 75 mg/m(2) were more common in patients from Asia (47.0%) than other regions (13.4%); docetaxel dose escalations to 100 mg/m(2) were less frequent in Asia (2.4%) than other regions (18.7%). Rates of edema (26.1% and 5.4% for Asia and other regions, respectively), myalgia (42.3%, 14.7%), nail disorder (39.9%, 15.1%), febrile neutropenia (18.6%, 7.1%), upper respiratory tract infection (25.7%, 10.2%), decreased appetite (47.0%, 19.1%), and rash (44.3%, 22.0%) were at least twice as high in Asia as in other regions. Adverse events did not result in a reduction in the median number of study treatment cycles administered in patients from Asia. Efficacy analyses per region showed hazard ratios similar to those of the whole intention-to-treat (ITT) population for progression-free survival (ITT: 0.63; Asia: 0.68; other regions: 0.61) and overall survival (ITT: 0.66; Asia: 0.64; other regions: 0.66).
  
  
  CONCLUSIONS
  Despite a higher proportion of docetaxel dose reductions in patients from Asia, survival benefits were comparable between regions. The benefit-risk profile of pertuzumab, trastuzumab, and docetaxel supports this regimen as the first-line therapy for patients with HER2-positive metastatic breast cancer from all geographic regions.
authors.affiliation: Washington Cancer Institute, MedStar Washington Hospital Center, Washington, D.C., USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Hematology and Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Veterans Memorial Medical Center, Cancer Research Center, Quezon City, Philippines; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Roche Products Ltd., Welwyn Garden City, United Kingdom; Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, New York, USA Sandra.M.Swain@MedStar.net.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
authors.affiliation: Washington Cancer Institute, MedStar Washington Hospital Center, Washington, D.C., USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Hematology and Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Veterans Memorial Medical Center, Cancer Research Center, Quezon City, Philippines; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Roche Products Ltd., Welwyn Garden City, United Kingdom; Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, New York, USA.
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
authors.affiliation: Washington Cancer Institute, MedStar Washington Hospital Center, Washington, D.C., USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Hematology and Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Veterans Memorial Medical Center, Cancer Research Center, Quezon City, Philippines; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Roche Products Ltd., Welwyn Garden City, United Kingdom; Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, New York, USA.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: Washington Cancer Institute, MedStar Washington Hospital Center, Washington, D.C., USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Hematology and Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Veterans Memorial Medical Center, Cancer Research Center, Quezon City, Philippines; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Roche Products Ltd., Welwyn Garden City, United Kingdom; Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, New York, USA.
authors.forename: Valorie
authors.initials: V
authors.lastname: Chan
authors.affiliation: Washington Cancer Institute, MedStar Washington Hospital Center, Washington, D.C., USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Hematology and Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Veterans Memorial Medical Center, Cancer Research Center, Quezon City, Philippines; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Roche Products Ltd., Welwyn Garden City, United Kingdom; Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Miles
authors.affiliation: Washington Cancer Institute, MedStar Washington Hospital Center, Washington, D.C., USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Hematology and Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Veterans Memorial Medical Center, Cancer Research Center, Quezon City, Philippines; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Roche Products Ltd., Welwyn Garden City, United Kingdom; Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, New York, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Knott
authors.affiliation: Washington Cancer Institute, MedStar Washington Hospital Center, Washington, D.C., USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Hematology and Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Veterans Memorial Medical Center, Cancer Research Center, Quezon City, Philippines; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Roche Products Ltd., Welwyn Garden City, United Kingdom; Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, New York, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Clark
authors.affiliation: Washington Cancer Institute, MedStar Washington Hospital Center, Washington, D.C., USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Hematology and Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Veterans Memorial Medical Center, Cancer Research Center, Quezon City, Philippines; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Roche Products Ltd., Welwyn Garden City, United Kingdom; Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, New York, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Ross
authors.affiliation: Washington Cancer Institute, MedStar Washington Hospital Center, Washington, D.C., USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Hematology and Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Veterans Memorial Medical Center, Cancer Research Center, Quezon City, Philippines; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Roche Products Ltd., Welwyn Garden City, United Kingdom; Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, New York, USA.
authors.forename: José
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D000077143:Docetaxel; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D054316:Biomarkers, Pharmacological; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab
keywords: Asia; Febrile neutropenia; HER2-positive metastatic breast cancer; Pertuzumab; Trastuzumab