Patient-reported outcomes (PROs) data from the progression-free survival (PFS) analysis of DESTINY-Breast03 suggest that health-related quality-of-life (HRQoL) was sustained with trastuzumab deruxtecan across prespecified global measures and cancer-specific subscales, in accordance with its efficacy benefit in patients with HER2-positive metastatic breast cancer. In a phase III DESTINY-Breast03 study, the median treatment duration was approximately twice as long with trastuzumab deruxtecan compared to trastuzumab emtansine, highlighting the importance of considering the effects of treatment on patients’ HRQoL.
In both treatment arms, the EORTC QLQ-C30 global health status (GHS)/QoL scale score, the primary PRO variable of interest in this study, did not show clinically significant change from baseline for the duration of treatment and follow-up, indicating that HRQoL was maintained on trastuzumab deruxtecan despite a longer treatment duration. The findings are published by Dr. Giuseppe Curigliano of the European Institute of Oncology IRCCS and University of Milan in Milan, Italy, and colleagues on 11 May 2023 in the Annals of Oncology.
In the first interim analysis of PFS from the DESTINY-Breast03 study, the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan demonstrated a clinically meaningful improvement in PFS and overall survival versus trastuzumab emtansine in patients with previously treated HER2-positive metastatic breast cancer. Consistent with the known safety profile of trastuzumab deruxtecan, treatment-emergent adverse events were manageable in the DESTINY-Breast03 study.
Apart from efficacy and safety metrics, PROs have become increasingly important ancillary measures in breast cancer clinical studies, given that both the disease and its treatments can negatively affect patients’ HRQoL. PRO endpoints incorporate patient self-assessments of symptoms and functional deficits into the risk/benefit analysis of a drug’s therapeutic value.
Hospital admission is another clinically important event that illustrates overall patient health and healthcare utilisation/costs. Assessing hospitalisation events can inform best practices for managing/reducing disease burden in at-risk individuals, thereby providing insights that may optimise monitoring and mitigate future hospital admissions and costs for healthcare services.
In the latest article published in the Annals of Oncology, the researchers present the health economics and outcomes research results from the first interim analysis of the DESTINY-Breast03 study, comparing the impact of trastuzumab deruxtecan and trastuzumab emtansine on PROs and hospitalisation events to determine the effect of treatment on patients’ HRQoL.
Patients included in the DESTINY-Breast03 study were assessed for prespecified PRO measures, including EORTC-QoL questionnaires, the oncology-specific EORTC QLQ-C30 and breast cancer-specific EORTC QLQ-BR45, and the generic EQ-5D-5L visual analogue scale. Analyses included change from baseline, time to definitive deterioration, and hospitalisation-related endpoints.
EORTC QLQ-C30 baseline GHS scores for trastuzumab deruxtecan (n = 253) and trastuzumab emtansine (n = 260) were similar, with no clinically meaningful change (<10-point change from baseline) while on either treatment; median treatment duration was 14.3 months for trastuzumab deruxtecan and 6.9 months for trastuzumab emtansine.
Time to definitive deterioration analyses of QLQ-C30 GHS (primary PRO variable) and all other prespecified PROs (QLQ-C30 subscales, the QLQ-BR45 arm symptoms scale, and the EQ-5D-5L visual analogue scale) suggested trastuzumab deruxtecan was numerically favoured over trastuzumab emtansine based on time to definitive deterioration hazard ratios.
Of all randomised patients, 18 (6.9%) receiving trastuzumab deruxtecan versus 19 (7.2%) receiving trastuzumab emtansine were hospitalised, and the median time to first hospitalisation was 219.5 versus 60.0 days, respectively.
The authors concluded that in DESTINY-Breast03, EORTC GHS/QoL was maintained on both therapies throughout treatment, indicating that despite the longer treatment duration with trastuzumab deruxtecan versus trastuzumab emtansine, HRQoL did not worsen on trastuzumab deruxtecan. Furthermore, time to definitive deterioration hazard ratios numerically favoured trastuzumab deruxtecan over trastuzumab emtansine in all prespecified variables of interest including pain, suggesting trastuzumab deruxtecan may delay time until HRQoL deterioration compared with trastuzumab emtansine. Median time to first hospitalisation was three times longer with trastuzumab deruxtecan versus trastuzumab emtansine.
Together with reported improved efficacy and manageable toxicity, these results support the overall benefit of trastuzumab deruxtecan for patients with HER2-positive metastatic breast cancer.
The study was supported by Daiichi Sankyo in collaboration with AstraZeneca.
Reference
Curigliano G, Dunton K, Rosenlund M, et al. Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase 3 DESTINY-Breast03 study. Annals of Oncology; Published online 11 May 2023. DOI: https://doi.org/10.1016/j.annonc.2023.04.516