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.

The median PFS in the HR+ cohort was 5.4 months in the chemotherapy group and 10.1 months in the Enhertu group (hazard ratio [HR] 0.51; 95% CI: 0.40, 0.64; p0.0001). In the Enhertu arm, the median PFS was 9.9 months (95% CI: 9.0, 11.3), whereas for those taking chemotherapy, it was 5.1 months (95% CI: 4.2, 6.8) (HR 0.50; 95% CI: 0.40, 0.63; p0.0001).

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. 

Susan Hau

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Susan Hau is a distinguished researcher in the field of cancer cell therapy, with a particular focus on T cell-based approaches and cancer vaccines. Her work spans several innovative treatment modalities, including CAR T-cell therapy, TIL (Tumor-Infiltrating Lymphocyte) therapy, and NK (Natural Killer) cell therapy.

Hau's expertise lies in cancer cell biology, where she has made significant contributions to understanding the complex interactions between immune cells and tumors.

Her research aims to enhance the efficacy of immunotherapies by manipulating the tumor microenvironment and exploring novel ways to activate and direct immune responses against cancer cells.

Throughout her career, Hau has collaborated with leading professors and researchers in the field of cancer treatment, both in the United States and China.

These international experiences have broadened her perspective and contributed to her innovative approach to cancer therapy development.

Hau's work is particularly focused on addressing the challenges of treating advanced and metastatic cancers. She has been involved in clinical trials evaluating the safety and efficacy of various immunotherapy approaches, including the promising Gamma Delta T cell therapy.

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