Quality of life in hormone receptor-positive HER-2+ metastatic breast cancer patients during treatment with letrozole alone or in combination with lapatinib

Abstract

Background: A phase III trial compared lapatinib plus letrozole (L + Let) with letrozole plus placebo (Let) as first-line therapy for hormone receptor (HR)(+) metastatic breast cancer (MBC) patients. The primary endpoint of progression-free survival (PFS) in patients whose tumors were human epidermal growth factor receptor (HER)-2(+) was significantly longer for L + Let than for Let (8.2 months versus 3 months; p = .019). This analysis focuses on quality of life (QOL) in the HER-2(+) population.

Methods: QOL was assessed at screening, every 12 weeks, and at withdrawal using the Functional Assessment of Cancer Therapy-Breast (FACT-B). Changes from baseline were analyzed and the proportions of patients achieving minimally important differences in QOL scores were compared. Additional exploratory analyses evaluated how QOL changes reflected tumor progression status.

Results: Among the 1,286 patients randomized, 219 had HER-2(+) tumors. Baseline QOL scores were comparable in the two arms. Mean changes in QOL scores were generally stable over time for patients who stayed on study. The average change from baseline on the FACT-B total score in both arms was positive at all scheduled visits through week 48. There was no significant difference between the two treatment arms in the percentage of QOL responders.

Conclusion: The addition of lapatinib to letrozole led to a significantly longer PFS interval while maintaining QOL during treatment, when compared with letrozole alone, thus confirming the clinical benefit of the combination therapy in the HR(+) HER-2(+) MBC patient population. This all oral regimen provides an effective option in this patient population, delaying the need for chemotherapy and its accompanying side effects.

Trial registration: ClinicalTrials.gov NCT00073528.

Figure 1.

Treatment group changes from baseline for FACT-B total, FACT-G, and TOI scores, HER-2+ population. Least squares mean changes (95% CI) from analysis of covariance, adjusted for baseline score. Bars indicate ± 1.96 standard error. Abbreviations: CI, confidence interval; FACT-B, Functional Assessment of Cancer Therapy–Breast; FACT-G, Functional Assessment of Cancer Therapy–General; HER-2, human epidermal growth factor receptor 2; L + Let, lapatinib + letrozole; Let, letrozole; MID, minimum important difference; TOI, trial outcome index.

Figure 2.

Adjusted mean change from baseline for FACT-B total scores, by progression status, HER-2⁺ population. Least squares mean changes (95% confidence interval) from analysis of covariance, adjusted for baseline score. Abbreviations: FACT-B, Functional Assessment of Cancer Therapy–Breast; HER-2, human epidermal growth factor receptor 2; MID, minimum important difference.

Figure 3.

Distribution of QOL response based on minimum important difference FACT-B change from baseline, by progression status, HER-2⁺ population. Declined represents decrease from baseline of ≥7 points; improved is ≥7-point increase from baseline. p-values are from Fisher's exact test using patients with baseline and postbaseline QOL scores. Abbreviations: FACT-B, Functional Assessment of Cancer Therapy–Breast; HER-2, human epidermal growth factor receptor 2; QOL, quality of life.