It is well recognized that patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have brain metastases have limited therapeutic choices and lower health-related quality of life compared with patients without brain metastases.1,2 To understand the impact of tucatinib (Tukysa) on health-related quality of life in patients with HER2-positive metastatic breast cancer with stable and active brain metastases, Andrew Wardley, MB ChB, MRCP, MSc, MD, FRCP, Medical Director, Breast Cancer Treatment and Research, National Institute for Health Research, Manchester Clinical Research Facility at The Christie, University of Manchester, United Kingdom, and colleagues provided insight from the latest findings of the HER2CLIMB clinical trial. In this study, patients with HER2-positive metastatic breast cancer that included patients with stable and active brain metastases were randomized 2:1 to receive tucatinib or placebo in combination with trastuzumab (Herceptin) and capecitabine (Xeloda).
Previously published findings of the HER2CLIMB study showed that the addition of tucatinib to trastuzumab plus capecitabine demonstrated a statistically significant and clinically meaningful improvement in the overall survival of patients with HER2-positive metastatic breast cancer and in those with stable and active brain metastases.3 Most importantly, the treatment had a tolerable and manageable safety profile.
In this evaluation, the impact of tucatinib on health-related quality of life in patients with stable and active brain metastases was assessed. Of the 612 patients included in the original analysis, health-related quality-of-life data were available from 330 patients; 163 of these patients presented with brain metastases.
The investigators used the EQ-5D-5L tool that includes a visual analog scale (EQ-VAS) and a descriptive system (EQ-5D) encompassing 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Health-related quality of life was assessed regularly, and every dimension was divided into 5 grades: no problems, slight problems, moderate problems, severe problems, and extreme problems. Data were gathered during cycle 1 at day 1; cycles 3 through 9 at every 2 cycles that were 21-day cycles in length; cycle 12 and beyond at every 3 cycles; and at the 30-day follow-up. For each treatment arm, the EQ-5D-5L scores were summarized by cycle. Time to deterioration was defined as a change that was >7 points from baseline on the EQ-VAS. For each arm, the median time to deterioration and 95% confidence intervals were calculated.
Overall, included in this health-related quality-of-life analysis were a total of 163 patients with active, stable brain metastases. In the tucatinib arm were 107 patients and included in the placebo arm were 56 patients. The tucatinib arm had an approximately 49% reduction in the risk of deterioration when compared with the placebo arm. With available follow-up, the median time to deterioration has not been reached in the tucatinib arm and was 5.5 months in the placebo arm. Once patients discontinued therapy, decline in all domains of the EQ-VAS and EQ-5D-5L scores were seen, particularly on the “usual activities” domain.
A significantly extended and clinically meaningful time to deterioration of health-related quality of life was observed in patients with metastatic breast cancer and brain metastases treated with tucatinib in combination with trastuzumab plus capecitabine. Throughout the treatment course, health-related quality of life was maintained, allowing patients to receive the full benefit of the therapeutic approach and resulting in statistically significant and clinically meaningful improvement in overall survival.
Source: Wardley A, Mueller V, Paplomata E, et al. Impact of tucatinib on health-related quality of life in patients with HER2+ metastatic breast cancer with stable and active brain metastases. Presented at: San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PD13-04.
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