Trastuzumab deruxtecan (T-DXd; Enhertu) demonstrates a significant reduction in pain deterioration and maintains quality of life (QOL) compared to treatment of physician's choice (TPC) in patients with hormone receptor–positive (HR+), HER2-low or -ultralow metastatic breast cancer (MBC). These findings, derived from patient-reported outcomes (PROs) in the DESTINY-Breast06 trial, were presented at the 2024 ESMO Congress, offering new insights into managing advanced breast cancer. The study highlights T-DXd's potential to improve patient well-being while providing effective disease control.
Key PRO Findings from DESTINY-Breast06
The multicenter, open-label, randomized phase 3 DESTINY-Breast06 trial included patients with HR+, HER2-low (defined as HER2 immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH]-negative) and HER2-ultralow (defined as HER2 IHC 0 with membrane staining) MBC. Patients had received at least two prior lines of endocrine therapy with or without targeted therapy, or had disease progression within 6 months of starting first-line endocrine therapy and a CDK4/6 inhibitor, or recurrence within 24 months after starting adjuvant endocrine therapy. Patients were randomized 1:1 to receive T-DXd (5.4 mg/kg every 3 weeks) or TPC (capecitabine, nab-paclitaxel, or paclitaxel).
Results from the DESTINY-Breast06 trial indicated that while the median time to deterioration (TTD) was similar between the T-DXd and TPC arms in the intent-to-treat (ITT) population and the HER2-low subgroup, significant differences emerged in specific symptoms. Notably, the median time to pain deterioration was markedly improved with T-DXd, reaching 22.0 months (95% CI, 17.2-not reached) compared to 6.3 months (95% CI, 4.8-9.6) for TPC (HR, 0.51; 95% CI, 0.39-0.65).
Impact on Quality of Life
According to Dr. Xichun Hu, MD, PhD, from Fudan University Shanghai Cancer Center, “The global health/QOL was observed over 31 weeks for both arms. The QOL scores did not change from the baseline to a clinically significant degree…Time to deterioration in QOL was similar with the 2 treatment arms. T-DXd reduced the risk of clinically meaningful deterioration in pain by 49%.”
The European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR45 questionnaires were used to assess patient-reported outcomes. The QLQ-C30 evaluated Global Health Status (GHS)/QOL, functional scales, and symptom scales. The QLQ-BR45 assessed multi-item scores including skin mycosis symptoms, body image, and breast symptoms. Overall GHS/QOL were maintained over 31 weeks in both arms, with no significant shifts from baseline. The median time to deterioration in GHS/QOL was 11.3 months for T-DXd and 10.5 months for TPC (HR, 0.93; 95% CI, 0.73-1.18).
Symptom Management and Adverse Events
Beyond pain reduction, T-DXd also reduced the risk of deterioration in physical functioning (HR, 0.72; 95% CI, 0.56-0.92), role functioning (HR, 0.75; 95% CI, 0.60-0.94), emotional functioning (HR, 0.71; 95% CI, 0.53-0.95), and fatigue (HR, 0.76; 95% CI, 0.61-0.93). However, T-DXd was associated with worse nausea/vomiting (HR, 1.60; 95% CI, 1.28-2.02), appetite loss (HR, 1.33; 95% CI, 1.05-1.69), and constipation (HR, 1.74; 95% CI, 1.34-2.27) compared to TPC.
Dr. Hu noted that the gastrointestinal (GI) symptoms reported by patients receiving T-DXd highlight the importance of implementing antiemetic prophylaxis. He added that these GI adverse events “did not appear to be detrimental to overall preservation of QOL and were consistent with the safety profile reported by study investigators.”
Clinical Implications
The primary analysis of the DESTINY-Breast06 trial demonstrated that T-DXd significantly improved progression-free survival compared to TPC (13.2 months vs 8.1 months; HR, 0.62; 95% CI, 0.51-0.74; P < .0001). The PRO results further support T-DXd as a valuable therapeutic option for patients with HER2-low and HER2-ultralow, HR+ MBC following one or more endocrine-based therapies.
