KEY TAKEAWAYS
- Fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd) has been approved by the US Food and Drug Administration for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer.
- The approval was based on the results of phase III,r DESTINY-Breast04 trial.
- The study met its primary efficacy end point of PFS in the hormone receptor-positive cohort, with an estimated HR of 0.51.
- Key secondary endpoints were also met, including PFS in the intent-to-treat population, OS in the HR+ cohort, and OS in the intent-to-treat population.
- The safety profile of T-DXd was consistent with previously approved indications, and no new safety signals were observed in this study population. This represents the first approved therapy specifically for treating HER2-low metastatic breast cancer.
Adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry 1+ or immunohistochemistry 2+/in situ hybridization-) breast cancer who have received prior chemotherapy in the metastatic setting or who have developed disease recurrence during or within 6 months of completing adjuvant chemotherapy has been approved to receive fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd)
DESTINY-Breast04, a phase III, randomized, open-label, multicenter trial in patients with unresectable or metastatic HER2-low breast cancer, as determined at a central laboratory, provided the data on which the approval was based. T-DXd 5.4 mg/kg intravenously every 3 weeks (n = 373) or physicians’ choice of chemotherapy (n = 184) was randomly allocated to a total of 557 patients (2:1).
The estimated hazard ratio (HR) in the hormone receptor-positive (HR+) group (N = 494) was 0.51 (95% confidence interval [CI], 0.40 to 0.64; P <.0001). This was the major efficacy end point of the trial. Overall survival (OS) in the HR+ cohort was 0.64 (95% CI, 0.48 to 0.86; P =.0028), and OS in the intent-to-treat group was 0.64 (95% CI, 0.49 to 0.84; P =.0010), demonstrating success in these secondary end criteria as well. T-safety DXd’s profile was consistent with its approved uses, and no new safety signals were noted in this population.
Being the first licensed drug for treating HER2-low metastatic breast cancer, T-DXd was approved on the basis of statistically significant and clinically relevant PFS and OS improvements reported in the DESTINY-Breast04 trial.
Source:https://pubmed.ncbi.nlm.nih.gov/36780610/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03734029
Narayan, P., Dilawari, A., Osgood, C., Feng, Z., Bloomquist, E., Pierce, W.F., Jafri, S., Kalavar, S., Kondratovich, M., Jha, P., Ghosh, S., Tang, S., Pazdur, R., Beaver, J.A. and Amiri-Kordestani, L. (2023). US Food and Drug Administration Approval Summary: Fam-Trastuzumab Deruxtecan-nxki for Human Epidermal Growth Factor Receptor 2-Low Unresectable or Metastatic Breast Cancer. Journal of Clinical Oncology. doi:https://doi.org/10.1200/jco.22.02447.
