title: Comparative effectiveness analysis of monotherapy with cytotoxic agents in triple-negative metastatic breast cancer in a community setting.
abstract: OBJECTIVE
  There has been considerable progress in the treatment of metastatic breast cancer. However, the identification of optimal cytotoxic agents in patients with triple-negative breast cancer (TNBC) (negative for hormone receptors and human epidermal growth factor receptor 2) remains a therapeutic challenge. We conducted a comparative effectiveness analysis of 4 cytotoxic agents in patients with TNBC.
  
  
  METHODS
  We retrospectively identified patients who received single-agent chemotherapy with eribulin, capecitabine, gemcitabine, or vinorelbine from 19 community oncology clinics across the United States. Data collection included baseline patient and disease characteristics, prior therapies, performance status, duration of current therapy, growth-factor use and other supportive care, and dose-limiting toxicities and associated dose reductions or delays or skipped doses. Time to treatment failure (TTF) was measured from the first cycle of chemotherapy until disease progression, discontinuation due to toxicity, or death. TTF was estimated using the Kaplan-Meier method and Cox proportional hazards modeling adjusted for clustering on the practice site. To control for selection bias, which is inherent in observational studies, a propensity score-weighted TTF analysis was also conducted.
  
  
  RESULTS
  Data from 225 patients were included in the analysis (eribulin, 47 patients; capecitabine, 69; gemcitabine, 56; and vinorelbine, 53). The median age of each group was <60 years, with the exception of the gemcitabine group (63 years). The 4 groups were comparable with respect to age, performance status, duration of disease-free survival, presence of comorbidities, and hemoglobin level before the start of chemotherapy. Median lines of therapy of eribulin, capecitabine, gemcitabine, and vinorelbine and were 4th, 2nd, 3rd, and 3rd, respectively. The median durations of treatment were ~2 months with eribulin, capecitabine, and gemcitabine compared with 1.6 months with vinorelbine. Using eribulin as the reference drug, and with adjustment for line of therapy and associated prognostic factors, the propensity score-weighted Cox regression analysis did not identify significant between-treatment differences in TTF (hazard ratios [95% CI] vs eribulin: capecitabine, 1.15 [0.75-1.76]; gemcitabine, 0.62 [0.34-1.13]; and vinorelbine, 1.0 [0.67-1.67]).
  
  
  CONCLUSIONS
  In this assessment of patients with TNBC treated in a community oncology setting, eribulin was utilized in later lines compared with the other agents. However, comparable drug activity was reported among the 4 agents.
authors.affiliation: Augmentium Pharma Consulting Inc, Toronto, Ontario, Canada. Electronic address: george@augmentium.com.
authors.forename: George
authors.initials: G
authors.lastname: Dranitsaris
authors.affiliation: Sylvester Comprehensive Care Center, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gluck
authors.affiliation: Eisai Inc, Woodcliff Lake, New Jersey.
authors.forename: Claudio
authors.initials: C
authors.lastname: Faria
authors.affiliation: Eisai Inc, Woodcliff Lake, New Jersey.
authors.forename: David
authors.initials: D
authors.lastname: Cox
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
authors.forename: Hope
authors.initials: H
authors.lastname: Rugo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069287:Capecitabine / Q000627:therapeutic use; D003603:Cytotoxins / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005663:Furans / Q000627:therapeutic use; D006801:Humans; D007659:Ketones / Q000627:therapeutic use; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases; D012189:Retrospective Studies; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014747:Vinblastine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077235:Vinorelbine; D000093542:Gemcitabine; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D000069287:Capecitabine; D003603:Cytotoxins; D003841:Deoxycytidine; D005663:Furans; D007659:Ketones; D018719:Erb-b2 Receptor Tyrosine Kinases; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine; C508053:ERBB2 protein, human; C490954:eribulin; D000095662:Polyether Polyketides
keywords: capecitabine; eribulin; gemcitabine; metastatic breast cancer; triple negative; vinorelbine