Based on results from the phase 3 DESTINY-Breast04 trial, the FDA has approved fam-trastuzumab deruxtecan-nxki as an intravenous infusion for patients with unresectable or metastatic HER2-low breast cancer.
The FDA has approved fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) as an intravenous infusion for patients with unresectable or metastatic HER2-low breast cancer, according to a press release from the FDA.1
This approval is based on results from the phase 3 DESTINY-Breast04 trial (NCT03734029) in which T-DXd showed a statistically significant and clinically meaningful improvement in overall survival (OS) vs chemotherapy in the indicated patients population. Results of the study were recently presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and subsequently published in the New England Journal of Medicine.2,3
“Today’s approval highlights the FDA’s commitment to be at the forefront of scientific advances, making targeted cancer treatment options available for more patients,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in the press release. “Having therapies that are specially tailored to each patient’s cancer subtype is a priority to ensure access to safe and innovative treatments.”
A total of 557 patients were enrolled to the trial and received either 5.4 mg/kg of T-DXd every 3 weeks (n = 373) or investigator-choice chemotherapy (n = 184). HER2-low was defined as those with an immunohistochemistry score of 1+ or 2+ and a negative result via in situ hybridization. Additionally, 88.7% of patients were hormone receptor positive and 11.3% were negative.
Median progression-free survival (PFS) in the overall cohort was 9.9 months (95% CI, 9.0-11.3) with T-DXd and 5.1 months (95% CI, 4.2-6.8) with chemotherapy (HR, 0.50; 95% CI, 0.40-0.63; P <.001). For patients hormone receptor–positive disease, the median PFS was 10.1 months (95% CI, 9.5-11.5) in the T-DXd arm and 5.4 months (95% CI, 4.4-7.1) in the chemotherapy arm (HR, 0.51; 95% CI, 0.40-0.64; P <.0001). For patients with hormone receptor–negative disease, the median PFS was 8.5 months (95% CI, 4.3-11.7) in the T-DXd arm and 2.9 months (95% CI, 1.4-5.1) in the chemotherapy arm (HR, 0.46; 95% CI, 0.24-0.89). Patients who received prior CDK4/6 inhibitor therapy and were hormone receptor positive had a median PFS of 10.0 months (95% CI, 8.3-11.4) in the T-DXd arm and 5.4 months (95% CI, 4.0-7.8) in the chemotherapy arm (HR, 0.55; 95% CI, 0.42-0.73).
In the overall population, median OS was 23.4 months (95% CI, 20.0-24.8) in the T-DXd group and 16.8 months (95% CI, 14.5-20.0) in the chemotherapy group (HR, 0.64; 95% CI, 0.49-0.84; P = .001). Patients who were hormone receptor positive had a median OS of 23.9 months (95% CI, 20.8-24.8) in the T-DXd arm and 17.5 months (95% CI, 15.2-22.4) in the chemotherapy arm (HR, 0.64; 95% CI, 0.40-0.86; P = .003). Additionally, those who were hormone receptor negative had a median OS of 18.2 months (95% CI, 13.6–not estimable) in the T-DXd arm and 8.3 months (95% CI, 5.6-20.6) in the chemotherapy arm (HR, 0.48; 95% CI, 0.24-0.95).
Patients remained on treatment for a median of 8.2 months in the T-DXd arm and 3.5 months in the chemotherapy arm. Patients discontinued treatment because of adverse effects at a rate of 16.2% with T-DXd vs 8.1% in the chemotherapy arm, with dose reductions in 22.6% vs 38.4%, respectively.
Treatment-emergent adverse effects (TRAEs) were experienced by patients in the T-DXd arm at a rate of 99.5% vs 98.3% in the chemotherapy arm, and serious AEs occurred in 27.8% vs 25.0% of patients, respectively. Frequent TRAEs of any-grade between both respective arms were nausea (73.0% vs 23.8%), fatigue (47.7% vs 42.4%), alopecia (37.7% vs 32.6%), vomiting (34.0% vs 9.9%), neutropenia (33.2% vs 51.2%), and anemia (33.2% vs 22.7%).
In the T-DXd arm, 14 patients deaths were determined to be related to AEs vs 5 in the chemotherapy arm. Interstitial lung disease in the T-DXd arm occurred in 5 patients at grade 3 and in 3 patients at grade 5.