title: Herceptin alone or in combination with chemotherapy in the treatment of HER2-positive metastatic breast cancer: pivotal trials.
abstract: Large pivotal phase II and III clinical trials investigated the therapeutic efficacy and safety of the humanized anti-HER2 monoclonal antibody, Herceptin, alone and in combination with standard chemotherapy, respectively, in HER2-positive metastatic breast cancer. Eligible patients were HER2 2+ and 3+ overexpressors, as determined by immunohistochemistry (IHC). Herceptin was well tolerated in both trials. Single-agent second/third-line Herceptin produced durable tumor responses. First-line Herceptin in combination with chemotherapy, in particular paclitaxel, significantly improved time to disease progression, duration of response and time to treatment failure. Combination therapy also provided a significant 25% improvement in overall survival. These clinical benefits have led to the approval of Herceptin for clinical use in the USA and elsewhere. Greater efficacy was noted in IHC 3+ patients compared with the overall population in both trials. Retrospective fluorescent in situ hybridization (FISH) testing of patient-tumor HER2 status revealed similar clinical outcomes in IHC 3+ and FISH-positive patients, consistent with the reported high concordance between IHC and FISH. Responses in the single-agent Herceptin trial were seen exclusively in FISH-positive patients. Approximately a quarter of HER2 2+ patients test FISH positive and may therefore benefit from therapy. Numerous studies are underway or planned to evaluate other Herceptin combinations and regimens in the metastatic and adjuvant settings.
authors.affiliation: Medical Oncology Service, Hospital General, Universitari Vall d'Hebron, Barcelona, Spain. baselga@hg.vhebron.es
authors.forename: J
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; 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; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis*; D017239:Paclitaxel / Q000008:administration & dosage; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012189:Retrospective Studies; D012449:Safety; D016037:Single-Blind Method; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D004317:Doxorubicin; D015251:Epirubicin; D009363:Neoplasm Proteins; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab