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

Abstract

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.

Trial registration: ClinicalTrials.gov identifier: NCT00075270.

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.

Key words::

• Cancer
• metastatic breast
• ErbB2+
• HER2
• Lapatinib
• Paclitaxel
• Q-TWiST
• Quality-of-life

Transparency

The EGF30001 study and analyses reported in this paper were funded by GlaxoSmithKline. One employee from GlaxoSmithKline participated with other co-authors in the interpretation of analysis results and in manuscript writing/review.

Declaration of financial/other relationships

M.A. is an employee of and holds stock in GlaxoSmithKline. B.S. and Y.W. are employees of RTI Health Solutions, a consultancy company that also has research consultancy contracts with several other pharmaceutical companies. B.S., A.D.L., Y.W. and H.G. have disclosed as serving as consultants to GlaxoSmithKline. A.D.L. has disclosed receiving honoraria from GlaxoSmithKline.

Acknowledgments

We thank the patients who participated in the study and their families; the medical, nursing, and research staff at the study centers; the independent data and safety monitoring committee; and the monitors, clinical operations staff, data managers, statisticians, and programmers at GlaxoSmithKline. We would also like to thank Michael Arbushites and Maria Koehler for their valuable assistance.

Previously presented in part at the 2008 San Antonio Breast Cancer Symposium (SABCS) 10–14 December 2008, San Antonio, Texas, and the 2009 American Society of Clinical Oncology (ASCO) annual meeting 29 May–2 June 2009, Orlando, FL, USA.