Quality-adjusted time without symptoms or toxicity analysis of trastuzumab deruxtecan versus trastuzumab emtansine in HER2- positive metastatic breast cancer patients based on secondary use of the DESTINY-Breast03 trial

Objective: DESTINY-Breast03, a randomised, phase 3 trial, evaluated trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor (HER2)-positive unresectable and/or metastatic breast cancer who progressed on or after treatment with trastuzumab and a taxane. At the current data cut off overall survival analysis, T-DXd demonstrated a substantial improvement in overall survival over T-DM1. This secondary analysis use of DESTINY-Breast03 aimed to further evaluate the treatment differences using quality-adjusted survival time without symptoms or toxicity (Q-TWiST) methods.

Methods: Patients' survival data was divided into three health states: time spent with grade 3-4 adverse events (TOX), time without adverse events before disease progression (TWiST), and time from disease progression to death (PROG). Mean health state duration was weighted by patients' mean utility score in each health state based on the EQ-5D-5L questionnaire and summed to obtain the Q-TWiST value. A threshold utility analysis was also conducted using a range of hypothetical utility scores to assess the impact on Q-TWiST values obtained.

Results: T-DXd was associated with a substantial and clinically important improvement in Q-TWiST compared to T-DM1 (mean difference = 3.80 months, 95 % CI: [1.91, 5.62], nominal P-value <0.001; relative gain = 11.64 %). The robustness of the results was supported by threshold utility analysis.

Conclusion: T-DXd produced a substantial improvement in quality-adjusted time without symptoms or toxicity when accounting for time on treatment exposure compared to T-DM1. Consequently, T-DXd is shown to improve both length and quality of life.