Preservation of quality of life in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer treated with tucatinib or placebo when added to trastuzumab and capecitabine (HER2CLIMB trial)

Abstract

Aims: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2epositive (HER2þ) metastatic breast cancer. We evaluated the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB. Methods: Patients were randomised 2:1 to tucatinib or placebo combined with trastuzumab and capecitabine. Starting with protocol version 7, the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire and EQ visual analogue scale (VAS) were administered at day 1 of cycle 1, every two cycles during cycles 3e9, every three cycles during cycle 12 and thereafter and at each patient's 30-day follow-up visit. Results: Among 364 patients eligible for HR-QoL assessment, 331 (91%) completed 1 assessment. EQ-VAS scores were similar for both arms at baseline and maintained throughout treatment. EQ-5D-5L scores were similar between the treatment arms, stable throughout therapy and worsened after discontinuing treatment. Risk of meaningful deterioration (7 points) on EQ-VAS was reduced 19% in the tucatinib vs. placebo arm (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.55, 1.18); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.8 months (4.3, -) in the placebo arm. Among patients with brain metastases (n Z 164), risk of meaningful deterioration on EQ-VAS was reduced 49% in the tucatinib arm (HR: 0.51; 95% CI: 0.28, 0.93); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.5 months (4.2, -) in the placebo arm. Conclusions: HR-QoL was preserved for patients with HER2þ metastatic breast cancer who were treated with tucatinib added to trastuzumab and capecitabine and maintained longer with tucatinib therapy than without it among those with brain metastases. Clinical Trial Registration: NCT02614794

Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis

“…Using the EuroQol 5 Dimensions 5 Levels instrument, the tucatinib combination was found to preserve health-related quality of life throughout treatment. 33 Finally, the proportions of patients who received additional anticancer therapies post-progression in tucatinib combination and placebo combination groups were high and comparable, suggesting that tucatinib combined with trastuzumab and capecitabine is sufficiently well tolerated for patients to receive additional treatments.…”

Neratinib and Capecitabine for the Treatment of Leptomeningeal Metastases from HER2-Positive Breast Cancer: A Series in the Setting of a Compassionate Program

“…The scenario is rapidly evolving after the investigation of tucatinib in the HER2CLIMB trial on HER2+ metastatic BC, which displayed superiority in all the planned outcomes, such as PFS, OS, objective response rate [ 36 ] and quality of life [ 37 ] including in patients with BM [ 38 ]. Recently, Murthy et al reported the results of a phase 2 TBCRC049 trial focused on 17 patients with LM from HER2-positive BC, who were treated with tucatinib, trastuzumab, and capecitabine: an i-PFS of 6.9 months (95% CI 2.3–13.8) and an OS of 10 months (95% CI 4.1-not reached) were observed [ 39 ].…”

Austrian treatment algorithms in HER2-positive metastatic breast cancer: a 2022 update

“…An evaluation of the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB demonstrated that HR-QoL was preserved for patients with HER2-positive mBC who were treated with tucatinib when added to trastuzumab and capecitabine. Additionally, HR-QoL was maintained longer with tucatinib therapy than with placebo among those with BM [ 11 ].…”