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 TherapyBreast (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 (LP) arm demonstrated stable FACT-B scores over the first year, while average scores for patients on Pplacebo (Ppla) monotherapy decreased (change from baseline: LP, p=0.99; Ppla, 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 LP 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, LP resulted in more stable QOL and more quality-adjusted survival than paclitaxel monotherapy, representing clinically important differences between treatments. © 2010 Informa UK Ltd All rights reserved.