Trastuzumab Deruxtecan Versus Chemotherapy: Efficacy by Disease Progression in DESTINY-Breast06

The DESTINY-Breast06 phase 3 trial showed that trastuzumab deruxtecan significantly improved progression-free survival in HR-positive, HER2-low, HER2-ultralow metastatic breast cancer.

Results from a recent phase 3 study, DESTINY-Breast06, demonstrated promising results for the treatment of hormone receptor (HR)-positive, HER2-low, and HER2-ultralow metastatic breast cancer (mBC). The study focused on patients who had experienced disease progression after at least 1 round of endocrine-based therapy and had not yet received chemotherapy for mBC. The trial investigated the effectiveness of trastuzumab deruxtecan (T-DXd) compared with treatment of physician’s choice (TPC). Results showed that T-DXd significantly improved progression-free survival (PFS) compared with TPC in HER2-low patients, with a median PFS of 13.2 months for T-DXd versus 8.1 months for TPC (P<0.0001).

Patients were assigned 1:1 to receive either T-DXd every 3 weeks or TPC. Outcomes included PFS, confirmed objective response rate (ORR), and duration of response (DOR) in the intention-to-treat (ITT) population. A total of 866 patients were enrolled in the ITT population. Researchers divided these patients based on their time to progression (TTP) on first-line (1L) therapy (<6 months 1L TTP, 6-12 months 1L TTP, >12 months 1L TTP). Interestingly, the PFS benefit of T-DXd was consistent across all TTP subgroups, including those who experienced rapid progression (defined as TTP <6 months). In the rapid-progression subgroup, the median PFS for T-DXd was 14 months, compared with only 6.5 months for those receiving TPC. These findings are particularly significant because patients with rapid progression typically have a poorer prognosis and fewer effective treatment options. The study also assessed the ORR and DOR. T-DXd consistently outperformed TPC in both ORR and DOR across all TTP subgroups, further solidifying its efficacy in this patient population.

The safety profile of T-DXd was consistent across the different TTP subgroups and in line with the overall safety observed in the study. The incidence of grade ≥3 treatment-emergent adverse events was similar between T-DXd and TPC in each subgroup. This suggests that the enhanced efficacy of T-DXd does not come at the cost of increased toxicity.

The DESTINY-Breast06 trial provides compelling evidence that T-DXd could be a valuable new tool in the treatment of HR-positive, HER2-low, and HER2-ultralow mBC. The drug’s ability to significantly improve PFS, even in patients with rapid disease progression, makes it a particularly promising option for this challenging patient population. These findings pave the way for further investigation into the potential role of T-DXd as an early-line treatment option for patients with HER2-low or HER2-ultralow mBC.

Source

Bardia A, et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physicians choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: additional analysis from DESTINY-Breast06. Presented at: San Antonio Breast Cancer Symposium. December 10, 2024; San Antonio, TX. Abstract SESS-3676.