Trastuzumab deruxtecan doubled progression-free survival (PFS) vs standard chemotherapy in patients with HER2-low metastatic breast cancer, according to findings from the DESTINY-Breast04 trial. These practice changing results were presented at the 2022 ASCO Annual Meeting.

“Our study shows that trastuzumab deruxtecan may be a new and highly effective targeted therapy option for this newly defined patient population,” said lead author Shanu Modi, MD, Memorial Sloan Kettering Cancer Center, NY, during her presentation.

The phase 3 DESTINY-Breast04 aimed to compare the efficacy and safety of trastuzumab deruxtecan vs standard chemotherapy in patients with metastatic breast cancer and low HER2 expression levels who received 1-2 prior lines of chemotherapy in the metastatic setting.

The primary end point of the trial was PFS in patients with hormone receptor (HR)–positive metastatic breast cancer, determined by blinded independent central review. Secondary end points included PFS in the full analysis set and overall survival (OS) in both patients with HR-positive disease and the full analysis set.

The trial randomized 557 patients in a 2:1 ratio to receive to trastuzumab deruxtecan (n = 373) or physician’s choice of standard chemotherapy (n = 184). In each arm, 88.7% and 88.6% of patients were HR-positive, respectively.

Median follow-up was 18.4 months (95% confidence interval (CI), 17.9 to 19.1). The median treatment duration was 8.2 months with trastuzumab deruxtecan and 3.5 months with standard chemotherapy.

In patients who were HER2-low and HR-positive, the median PFS was 10.1 months with trastuzumab deruxtecan vs 5.4 months with standard chemotherapy (hazard ratio, 0.51; 95% CI, 0.40 to 0.64; P <.0001). Median OS in this subgroup was 23.9 months vs 17.5 months, respectively (HR, 0.64; 95% CI, 0.48 to 0.86; P = .0028).

In the full analysis set, the median PFS was 9.9 months with trastuzumab deruxtecan vs 5.1 months with standard chemotherapy (HR, 0.50; 95% CI, 0.40 to 0.63; P <.0001). Median OS was 6.6 months and 2.9 months, respectively (HR, 0.64; 95% CI, 0.49 to 0.84; P = .0010).

Overall, 52.6% of patients in the trastuzumab deruxtecan arm vs 67.4% of patients in the standard chemotherapy arm experienced grade ≥3 treatment–emergent adverse events. Independently adjudicated drug–related interstitial lung disease/pneumonitis was reported in 45 patients in the trastuzumab deruxtecan arm vs 1 patient in the standard chemotherapy arm.

“DESTINY-Breast04 is the first phase 3 trial of a HER2-directed therapy in pts with HER2-low [metastatic breast cancer] to show a statistically significant and clinically meaningful benefit in PFS and OS compared to standard-of-care treatment, regardless of HR status, with a generally manageable safety profile,” concluded Dr Modi and colleagues.

Source:

Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study. Presented at: the 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract LBA3.