title: Final Results of the Randomized Phase II NorCap-CA223 Trial Comparing First-Line All-Oral Versus Taxane-Based Chemotherapy for HER2-Negative Metastatic Breast Cancer.
abstract: BACKGROUND
  The purpose of this study was to evaluate the efficacy of 3 first-line chemotherapy combination regimens for HER2-negative metastatic breast cancer (mBC).
  
  
  METHODS
  In this open-label, 3-arm, randomized phase II trial, patients were randomized to all-oral NORCAP (vinorelbine/capecitabine), GEMPAC (gemcitabine/paclitaxel), or GEMDOC (gemcitabine/docetaxel) as first-line chemotherapy for HER2-negative mBC. Stratification factors were center, previous (neo)adjuvant anthracycline, and age. The primary end point was disease control rate (DCR; complete or partial response, or stable disease for ≥3 months).
  
  
  RESULTS
  The DCR was 73% (95% confidence interval [CI], 59-85) with NORCAP (36 of 49 patients), 78% (95% CI, 64-88) with GEMPAC (39 of 50 patients), and 80% (95% CI, 66-90) with GEMDOC (40 of 50 patients). Objective response rates were 33% (16 of 49 patients), 24% (12 of 50 patients), and 50% (25 of 50 patients), respectively; median progression-free survival was 7.6, 9.0, and 11.4 months, respectively. Median overall survival was 30 to 31 months with all regimens. The most common Grade ≥3 adverse event with each regimen was neutropenia (24 patients [50%], 23 patients [46%], and 43 patients [86%], respectively). The most common nonhematological Grade ≥3 adverse event was fatigue. Grade 2 alopecia occurred in 36 patients (72%) who received GEMPAC and 38 patients (76%) who received GEMDOC, but only 4 patients (8%) who received NORCAP. There was no evidence of a detrimental effect of NORCAP on quality of life.
  
  
  CONCLUSIONS
  All-oral NORCAP is an active first-line chemotherapy regimen and might be offered as an alternative to first-line taxane-based therapy for HER2-negative mBC, particularly if patients wish to avoid alopecia or frequent intravenous administrations.
authors.affiliation: Medical Oncology and Breast Unit, European Institute of Oncology (IRCCS), Milan, and San Antonio Perrino Hospital, Brindisi, Italy. Electronic address: saverio.cinieri@ieo.it.
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinieri
authors.affiliation: Breast Cancer Research Centre-WA and Curtin University, Perth, Australia.
authors.forename: Arlene
authors.initials: A
authors.lastname: Chan
authors.affiliation: Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
authors.forename: Kadri
authors.initials: K
authors.lastname: Altundag
authors.affiliation: Medical Oncology Department, ZNA Middelheim Hospital, Antwerp, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Vandebroek
authors.affiliation: Centre Hospitalier Universitaire de Limoges, Limoges, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Tubiana-Mathieu
authors.affiliation: Medical Oncology Department, Hospital Sant Pau, Barcelona, Spain.
authors.forename: Agusti
authors.initials: A
authors.lastname: Barnadas
authors.affiliation: Medical Oncology Department, CER Instituto Medico, Buenos Aires, Argentina.
authors.forename: Patricia
authors.initials: P
authors.lastname: Dodyk
authors.affiliation: Medical Oncology Department, Istituti Ospitalieri di Cremona, Cremona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lazzarelli
authors.affiliation: Department of Oncology, National Hospital, Bloemfontein, South Africa.
authors.forename: Michiel
authors.initials: M
authors.lastname: Botha
authors.affiliation: Medical Oncology Department, Regionalspital Thun, Thun, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauch
authors.affiliation: Medical Affairs Oncology, Institut de Recherche Pierre Fabre, Boulogne-Billancourt Cedex, France.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Villanova
authors.affiliation: Department of Medical Oncology, Gazi University School of Medicine, Gazi Hospital, Ankara, Turkey.
authors.forename: Ugur
authors.initials: U
authors.lastname: Coskun
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine / Q000008:administration & dosage / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D000077143:Docetaxel; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011788:Quality of Life; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000069287:Capecitabine; D003841:Deoxycytidine; D000077143:Docetaxel; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine; C508053:ERBB2 protein, human
keywords: Capecitabine; Combination chemotherapy; Oral chemotherapy; Oral vinorelbine; Taxane doublet