FDA Approves Trastuzumab Deruxtecan for Patients With HER2-Low Breast Cancer

The Food and Drug Administration (FDA) granted approval to fam-trastuzumab deruxtecan-nxki, a HER2-directed antibody and topoisomerase inhibitor conjugate to be administered intravenously, to treat adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-low breast cancer who have previously received chemotherapy in the metastatic setting or have developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.

The approval was based on the ongoing phase 3 DESTINY-Breast04 trial, which has enrolled 557 patients with unresectable or metastatic HER2-low breast cancer separated into 2 cohorts: hormone receptor-positive [HR+] patients (n = 494) and hormone receptor-negative [HR-negative] patients (n = 63) as of the data cut-off date of January 26, 2022. HER2-low expression was defined as IHC 1+ or IHC 2+/ISH- in the trial.

Patients were randomized on a 2:1 basis to receive either fam-trastuzumab deruxtecan-nxki 5.4 mg/kg  by intravenous infusion every 3 weeks (n = 373) or chemotherapy (N = 184, including eribulin, capecitabine, gemcitabine, nab-paclitaxel, or paclitaxel). The primary outcome was progression-free survival (PFS) in the HR+ cohort. Secondary outcomes included PFS in the overall population (all randomized HR+ and HR-negative patients), overall survival (OS) in the HR+ cohort, and OS in the overall population.

In the fam-trastuzumab deruxtecan-nxki arm of the HR+ cohort, median PFS was 10.1 months (95% confidence interval [CI], 9.5 to 11.5) vs 5.4 months (95% CI, 4.4 to 7.1) for those treated with chemotherapy (hazard ratio [HR] 0.51; 95% CI, 0.40 to 0.64; p<.0001). Median OS was 23.9 months (95% CI, 20.8 to 24.8) in the fam-trastuzumab deruxtecan-nxki arm vs 17.5 months (95% CI, 15.2 to 22.4) in the chemotherapy arm (HR 0.64; 95% CI, 0.48 to 0.86; p=.0028).

In the overall population, median PFS in the fam-trastuzumab deruxtecan-nxki arm was 9.9 months (95% CI, 9 to 11.3) vs 5.1 months (95% CI, 4.2 to 6.8) in the chemotherapy arm (HR 0.50; 95% CI, 0.4 to 0.63; p<.0001), and the median OS was 23.4 months (95% CI, 20.0 to 24.8) and 16.8 months (95% CI, 14.5 to 20.0) in the fam-trastuzumab deruxtecan-nxki and chemotherapy arms, respectively (HR 0.64; 95% CI, 0.49 to 0.84; p=.001).

In the fam-trastuzumab deruxtecan-nxki arm, more than 20% of patients experienced treatment-related adverse events (AEs). The most common AEs were nausea, fatigue, alopecia, vomiting, anemia, constipation, decreased appetite, diarrhea, and musculoskeletal pain. The prescription includes a black box warning for interstitial lung disease and embryo-fetal toxicity.

Source:

FDA approves fam-trastuzumab deruxtecan-nxki for HER2-low breast cancer. Press Release. United States Food and Drug Administration. August 5, 2022. Accessed August 8, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-her2-low-breast-cancer/