title: Impact of lapatinib plus trastuzumab versus single-agent lapatinib on quality of life of patients with trastuzumab-refractory HER2+ metastatic breast cancer.
abstract: BACKGROUND
  Progression-free survival (PFS) was significantly longer for the lapatinib plus trastuzumab (L+T) arm than for L alone in a phase III, randomized, open-label study of women with human epidermal growth factor receptor 2 positive metastatic breast cancer who had documented progression on at least one T-containing regimen in the metastatic setting. This analysis focused on impact of treatments on health-related quality of life (HRQOL).
  
  
  METHODS
  HRQOL was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. Changes from baseline and time to deterioration were analyzed in the intent-to-treat population.
  
  
  RESULTS
  Differences between the treatment arms in adjusted mean change from baseline favored the L+T arm, ranging from 0.0 to 4.1 (FACT-B), 1.0-4.0 [Functional Assessment of Cancer Therapy-General (FACT-G)], and 0.5-2.7 (Trial Outcome Index). Most differences were not statistically significant, except for FACT-G at week 12 (delta = 4.0, P = 0.037). Similar results were found in a sensitivity analysis that included HRQOL records up to patient withdrawal from original randomized treatment. The longer time to HRQOL deterioration in the L+T arm was not statistically significant (FACT-B hazard ratio, 0.82; 95% confidence interval 0.56-1.20).
  
  
  CONCLUSIONS
  The addition of lapatinib to trastuzumab prolonged PFS while improving or maintaining near-term HRQOL, suggesting a meaningful clinical benefit to patients.
authors.affiliation: Biometrics Department, Research Triangle Institute Health Solutions, Research Triangle Park. Electronic address: ywu@rti.org.
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Global Health Outcomes, Oncology, GlaxoSmithKline, Collegeville.
authors.forename: M M
authors.initials: MM
authors.lastname: Amonkar
authors.affiliation: Biometrics Department, Research Triangle Institute Health Solutions, Research Triangle Park.
authors.forename: B H
authors.initials: BH
authors.lastname: Sherrill
authors.affiliation: Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, USA.
authors.forename: J
authors.initials: J
authors.lastname: O'Shaughnessy
authors.affiliation: Global Health Outcomes, Oncology, GlaxoSmithKline, Collegeville.
authors.forename: C
authors.initials: C
authors.lastname: Ellis
authors.affiliation: Medical Oncology Service, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Baselga
authors.affiliation: Duke University Medical Center, Durham.
authors.forename: K L
authors.initials: KL
authors.lastname: Blackwell
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Burstein
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077341:Lapatinib; D009362:Neoplasm Metastasis; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011795:Surveys and Questionnaires; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human