Fam-trastuzumab deruxtecan-nxki (Enhertu; Daiichi Sankyo) has been approved by FDA officials for use in patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, who have progressed on one or more endocrine therapies in the metastatic setting.1
FDA officials also approved Ventana’s PATHWAY anti-HER2 (4B5) Rabbit Monoclonal Primary Antibody assay as a companion diagnostic device to identify patients with HER2-ultralow (IHC 0 with membrane staining) breast cancer for treatment with fam-trastuzumab deruxtecan-nxki.
The approval was based on data derived from DESTINY-Breast06 (NCT04494425), a multicenter, open-label trial in 866 adult patients with advanced or metastatic HR-positive breast cancer with HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) expression as determined by the PATHWAY assay who had been evaluated at a central laboratory. The patients were randomly assigned to receive either fam-trastuzumab deruxtecan-nxki 5.4 mg/kg (N=436) by intravenous infusion every 3 weeks or physician’s choice of single-agent chemotherapy (N=430, capecitabine 60%, nab-paclitaxel 24%, or paclitaxel 16%).
The trial demonstrated a statistically significant improvement in progression-free survival (PFS) in patients with HER2-low breast cancer (n=713). Median PFS was 13.2 months in the fam-trastuzumab deruxtecan-nxki arm and 8.1 months in the chemotherapy arm (hazard ratio, 0.62; 95% confidence interval [CI], 0.52-0.75; P<.0001). The trial also demonstrated a statistically significant improvement in PFS in the overall population. Median PFS was 13.2 months and 8.1 months in the fam-trastuzumab deruxtecan-nxki and chemotherapy arms, respectively (hazard ratio, 0.64; 95% CI, 0.54-0.76; P<.0001). At the time of the PFS final analysis, overall survival data were immature, and a total of 335 (39%) patients had died across both trial arms in the overall population.
The most common adverse reactions (≥20%), including laboratory abnormalities, were decreased white blood cell count, decreased neutrophil count, nausea, decreased hemoglobin, decreased lymphocyte count, fatigue, decreased platelet count, alopecia, increased alanine aminotransferase, increased blood alkaline phosphatase, increased aspartate aminotransferase, decreased blood potassium, diarrhea, vomiting, constipation, decreased appetite, COVID-19 infection, and musculoskeletal pain.
Reference
- FDA. FDA approves fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HR-positive, HER2-low or HER2-ultralow breast cancer. January 27, 2025. Accessed February 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-hr-positive-her2-low-or-her2