title: First-line Herceptin monotherapy in metastatic breast cancer.
abstract: The pivotal phase II and III Herceptin trials proved the efficacy and safety of second- or third-line single-agent Herceptin and first-line Herceptin in combination with chemotherapy, respectively. In the current trial, 114 patients were randomized to one of two dose groups of first-line Herceptin monotherapy: standard dose of 4 mg/ kg initial dose followed by 2 mg/kg intravenous (i.v.) weekly; or high dose of 8 mg/kg initial dose followed by 4 mg/kg i.v. weekly. The regimen was generally well tolerated. A similar incidence of adverse events was demonstrated in the two dose groups with the possible exception of acute infusion-related events such as fever and chills as well as rash and dyspnea, which appear to be more prevalent in the higher dose group. The overall response rate was 26% and response rates were similar between the two dose groups (24% for the standard Herceptin dose group and 28% for the high Herceptin dose group). Subgroup analysis determined a higher response rate in IHC 3+ patients (35%) and FISH-positive patients (41%). When women with stable disease for > or =6 months were included with responders, the clinical benefit rate in IHC 3+ patients was 47%. Median survival was 24.4 months, which is comparable with the survival rate seen in the pivotal phase III combination trial (25 months). Therefore, single-agent Herceptin is an important new option for the first-line treatment of HER2-positive metastatic breast cancer patients.
authors.affiliation: University of Miami School of Medicine, Comprehensive Cancer Research Group, Inc, and Columbia Cancer Research Network of Florida, Miami, Fla, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Vogel
authors.forename: M A
authors.initials: MA
authors.lastname: Cobleigh
authors.forename: D
authors.initials: D
authors.lastname: Tripathy
authors.forename: J C
authors.initials: JC
authors.lastname: Gutheil
authors.forename: L N
authors.initials: LN
authors.lastname: Harris
authors.forename: L
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: D J
authors.initials: DJ
authors.lastname: Slamon
authors.forename: M
authors.initials: M
authors.lastname: Murphy
authors.forename: W F
authors.initials: WF
authors.lastname: Novotny
authors.forename: M
authors.initials: M
authors.lastname: Burchmore
authors.forename: S
authors.initials: S
authors.lastname: Shak
authors.forename: S J
authors.initials: SJ
authors.lastname: Stewart
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005334:Fever / Q000139:chemically induced; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis; D010146:Pain / Q000821:virology; D010166:Palliative Care; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D012449:Safety; D016879:Salvage Therapy; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D000068878:Trastuzumab