Quality-of-life and quality-adjusted survival (Q-TWiST) in patients receiving lapatinib in combination with paclitaxel as first-line treatment for metastatic breast cancer

Curr Med Res Opin. 2010 Apr;26(4):767-75. doi: 10.1185/03007991003590860.


Background: In a phase 3 randomized, multicenter, double-blind, placebo-controlled study, first-line therapy with lapatinib plus paclitaxel significantly improved clinical outcomes based on a pre-planned analysis of ErbB2+ metastatic breast cancer patients (GSK Study #EGF30001; ClinicalTrials.gov identifier: NCT00075270). Patients with ErbB2- or untested did not significantly benefit. This article focuses on the quality of life (QOL) and quality-adjusted survival outcomes (Q-TWiST) in the study.

Methods: QOL was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B). Changes from baseline were analyzed using ANCOVAs, repeated measures and pattern mixture modeling. The Q-TWiST method was used to examine the trade-off between toxicities and delayed progression.

Results: The study included 579 subjects, of whom 86 were ErbB2+. In the ITT population, no significant differences in QOL or Q-TWiST scores were observed. In the ErbB2+ subgroup, the lapatinib plus paclitaxel (L + P) arm demonstrated stable FACT-B scores over the first year, while average scores for patients on P + placebo (P + pla) monotherapy decreased (change from baseline: L + P, p = 0.99; P + pla, p = 0.01). Clinically meaningful differences were observed between treatment arms on the FACT-B, Trial Outcome Index and breast cancer subscale scores. Pattern mixture models suggested more QOL differentiation between treatments among patients who progressed or withdrew early. Q-TWiST differences between the arms in the ErbB2+ subgroup ranged from 2 to 15 weeks with an L + P advantage across all utility weight combinations.

Conclusions: In the ITT population, results provide no evidence of QOL differences between treatment groups. In a small, prospectively-defined subgroup of ErbB2+ patients, L + P resulted in more stable QOL and more quality-adjusted survival than paclitaxel monotherapy, representing clinically important differences between treatments.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Health Status*
  • Humans
  • Lapatinib
  • Neoplasm Metastasis
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Quality of Life*
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Receptor, ErbB-2


  • Quinazolines
  • Lapatinib
  • Receptor, ErbB-2
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT00075270