Fam-trastuzumab deruxtecan-nxki is approved by FDA for HER2-low breast cancer

August 2022: For adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH) breast cancer who have received prior chemotherapy in the metastatic setting or experienced a disease recurrence during or within six months of finishing adjuvant chemotherapy, the Food and Drug Administration has approved fam-trastuzumab deruxtecan-nxki (Enhertu, Daiichi Sankyo, Inc.).

DESTINY-Breast04 (NCT03734029), a randomised, multicenter, open-label clinical study that enrolled 557 patients with metastatic or unresectable HER2-low breast cancer, served as the foundation for the effectiveness analysis. In the study, there were two cohorts: 494 individuals with hormone receptor positivity (HR+) and 63 patients with hormone receptor negativity (HR-negative). In a centralised laboratory, IHC 1+ or IHC 2+/ISH- was used to characterise HER2-low expression. Enhertu 5.4 mg/kg was administered intravenously every three weeks to patients who were randomly assigned (2:1) to receive it or the physician’s choice of chemotherapy (N=184, including eribulin, capecitabine, gemcitabine, nab-paclitaxel, or paclitaxel).

The progression-free survival (PFS) rate in patients with HR+ breast cancer, as determined by a blinded independent central review using RECIST 1.1, served as the key effectiveness measure. PFS in the total population (all randomised HR+ and HR-negative patients), overall survival (OS) in HR+ patients, and OS in the total population were secondary effectiveness endpoints.

Patients’ ages ranged from 28 to 81, with 57 being the median, while 24% were 65 or older. The following list of selected demographics was provided: 99.6% of the population is female, 48% are White, 40% are Asian, 2% are Black or African Americans, and 3.8% are Hispanic/Latino.

In the HR+ cohort, the median OS for the chemotherapy and Enhertu arms, respectively, was 17.5 months (95% CI: 15.2, 22.4) and 23.9 months (95% CI: 20.8, 24.8) (HR 0.64; 95% CI: 0.48, 0.86; p=0.0028). In the general population, the median OS for the Enhertu group was 23.4 months (95% CI: 20.0, 24.8) and for the chemotherapy group, it was 16.8 months (95% CI: 14.5, 20.0) (HR 0.64; 95% CI: 0.49, 0.84; p=0.001).

In this trial, individuals who received Enhertu most frequently had nausea, fatigue, alopecia, vomiting, anaemia, constipation, decreased appetite, diarrhoea, and musculoskeletal pain. A Boxed Warning alerting medical professionals to the possibility of embryo-fetal harm and interstitial lung disease is included in the prescribing information.

Breast cancer patients should receive 5.4 mg/kg of Enhertu as an intravenous infusion once every three weeks (on a 21-day cycle) until the disease progresses or there is unacceptable toxicity.

View full prescribing information for Enhertu.