title: Quality-adjusted survival analysis of first-line treatment of hormone-receptor-positive HER2+ metastatic breast cancer with letrozole alone or in combination with lapatinib.
abstract: OBJECTIVE
  Compare first-line lapatinib plus letrozole (L + Let) versus letrozole monotherapy (Let) in hormone-receptor-positive HER2 + metastatic breast cancer, employing Q-TWiST (quality-adjusted time without symptoms and toxicity) analysis to account for differences in progression times, with offsets for the impact of adverse events during the treatment period.
  
  
  METHODS
  The area under survival curves for each treatment group was partitioned into distinct health states of varying utility: toxicity (TOX), time without toxicity or disease progression (TWiST), and the period following disease progression until death or end of follow-up (REL). The utility-weighted sum of the mean health state durations was derived for each group. The threshold utility analysis evaluates how varying utility values across the states affects Q-TWiST differences between groups, although the method is limited by not varying utilities within each health state.
  
  
  RESULTS
  The primary analysis population was the HER2 + subgroup (n = 219). There was no significant difference between treatments in mean duration of grade 3/4 adverse events prior to progression (L + Let = 1.95 weeks; Let = 2.14 weeks; P = 0.90). Using utility weights of 0.5 for TOX and REL, L + Let was favored for quality-adjusted survival by 8.8 weeks (P = 0.09). The Q-TWiST difference between treatment groups ranged from 8 to 9.5 weeks, favoring combination therapy for all hypothetical utility levels, but none of the comparisons were statistically significant at P = 0.05.
  
  
  CONCLUSIONS
  No significant differences were found between L + Let versus Let in mean duration of severe adverse events. Quality-adjusted survival was favored for the combination treatment arm for all utility levels examined when toxicity was defined by grade 3/4 AEs, but differences between groups were not statistically significant.
authors: RTI Health Solutions, Research Triangle Park, NC, USA. bsherrill@rti.org
authors: Beth
authors: B
authors: Sherrill
authors: Bintu
authors: B
authors: Sherif
authors: Mayur M
authors: MM
authors: Amonkar
authors: Julie
authors: J
authors: Maltzman
authors: Lisa
authors: L
authors: O'Rourke
authors: Stephen
authors: S
authors: Johnston
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077341:Lapatinib; D000077289:Letrozole; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases; D015996:Survival Rate; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D000077289:Letrozole; D009570:Nitriles; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D014230:Triazoles; C508053:ERBB2 protein, human