• Among rapid progressors, 50% of patients treated with T-DXd showed response vs none of the patients treated with TPC; this subgroup also had prolonged median PFS with T-DXd vs TPC, although interpreting this finding is limited by the small sample sizes
• Subgroups in general showed OS benefit based on the hazard ratio between T-DXd and TPC, consistent with the primary analyses; however, median OS was not reached for many subgroups (few OS events in the subgroups [data not shown])

The results of DESTINY-Breast04 HEOR analyses suggest T-DXd treatment delays the deterioration of GHS/QoL and shows a QoL benefit of T-DXd vs TPC in patients with HR+/HER2-low metastatic BC³3.Ueno N, Jacot W, Yamashita T, et al. Patient-reported outcomes from DESTINY-Breast04, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice in patients with HER2-low metastatic breast cancer [presentation and supplement]. Presented at: European Society for Medical Oncology (ESMO) 2022; September 9-13, 2022; Paris, France. Ann Oncol. 2022;33(suppl 7). Abs 217O.

• Overall GHS/QoL in DESTINY-Breast04 was maintained for patients in the HR+ cohort during the entire treatment period of T-DXd (8.2 months) or TPC (3.5 months)¹1.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [article]. N Engl J Med. 2022;387:9-20

• Mean change from baseline for QLQ-C30 GHS remained stable with T-DXd up to 27 cycles and with TPC up to 13 cycles

• The impact of T-DXd over time on nausea and vomiting was worse compared to TPC; however, with T‑DXd, an increase in nausea and vomiting scores was only clinically significant in early cycles

• Change from baseline in fatigue symptoms were similar between T-DXd and TPC and did not worsen over time with T-DXd

• The hazard ratios for TDD favored T-DXd over TPC for almost all PRO variables of interest (range, 0.40-0.73), including pain symptoms (hazard ratio, 0.40)

• The QoL benefit observed from the patient’s perspective confirm the efficacy and safety results of DESTINY-Breast04

• Significant concordance between central and historical results was observed despite the lack of prior clinical utility for HER2-low, the lack of pathologist training for distinguishing HER2 IHC 0 from HER2-low (IHC 1+, 2+/ISH−), evolving testing guidelines since historical HER2 status provision, differences in local testing methods, and differences in key sample characteristics
• The observed concordance rate is comparable to the reported initial concordance rates for HER2 positive (overexpression) IHC testing (range, 74%-82%)^5,65.Perez EA, Suman VJ, Davidson NE, et al. HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol. 2006;24(19):3032-3038.6.Roche PC, Suman VJ, Jenkins RB, et al. Concordance between local and central laboratory HER2 testing in the breast intergroup trial N9831. J Natl Cancer Inst. 2002;94(11):855-857.
• Concordance with prior HER2-low status was associated with region and collection date; the lowest concordance was observed for samples collected in/prior to 2013