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)

Eur J Cancer. 2021 Aug:153:223-233. doi: 10.1016/j.ejca.2021.05.025. Epub 2021 Jun 29.

Abstract

Aims: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2-positive (HER2+) 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 3-9, 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 = 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 HER2+ 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.

Keywords: Brain metastases; Human epidermal growth factor receptor 2 positive (HER2); Metastatic breast cancer; Quality of life; Trastuzumab; Tucatinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Capecitabine / pharmacology
  • Capecitabine / therapeutic use*
  • Female
  • Humans
  • Middle Aged
  • Oxazoles / pharmacology
  • Oxazoles / therapeutic use*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Quality of Life
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use*
  • Receptor, ErbB-2 / metabolism*
  • Trastuzumab / pharmacology
  • Trastuzumab / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Oxazoles
  • Pyridines
  • Quinazolines
  • tucatinib
  • Capecitabine
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab

Associated data

  • ClinicalTrials.gov/NCT02614794