Another Targeted Breast Cancer Drug Added: Trastuzumab Deruxtecan

Fam-trastuzumab deruxtecan-nxki (Enhertu) received accelerated approval for adults previously given at least 2 lines of anti-HER2-based treatment with unresectable or metastatic, HER2-positive breast cancer, on 20 December 2019 from the US Food and Drug Administration (FDA).

Approval rests on updated findings presented at the 2019 San Antonio Breast Cancer Symposiumfrom phase II DESTINY-Breast01 .

Trastuzumab deruxtecan resembles the previously standard HER2 breast cancer agent T-DM1 (Kadcyla) . Linking chemotherapy to an anti-HER2 monoclonal antibody, it is an antibody–chemotherapy conjugate.

The phase II study included heavily treated patients, averaging 6 lines, totaling 180 (%100 trastuzumab, %100 pertuzumab, %65.8 T-DM1). Median age was 56 (28-96).

FDA Oncology Center of Excellence director and deputy director of the Office of Oncologic Diseases, Dr. Richard Pazdur, stated: “Since Herceptin (trastuzumab) entered the market in 1998 , HER2-positive breast cancer drug development has advanced greatly. Enhertu offers the newest option after progression on existing HER2-targeted treatments. Targeted drug development rests on scientific understanding of malignant disease, in breast cancer and many other conditions.” 

Study Results

• Trastuzumab deruxtecan produced % 60.3 objective response , including % 4.3 complete response and % 56 partial response. In 67 patients (% 36.4), disease was stable; only 3 (% 1.6) progressed. Another 2 were unevaluable.
• On 1 August 2019, 79 patients (% 42.9) remained treated; 105 (% 57.1) discontinued, % 28.8 due to progression.
• Progression-free survival was 16 months. Average overall survival was not yet available, but 1-year survival was high at % 86.4. 
• Subgroup analysis of brain metastasis in 24 patients showed median time to worsening of 18 months.
• Adverse Effects: FDA assessed safety pooled from DESTINY-Breast01 and Study DS8201-A-J101 in 234 patients. In DESTINY-Breast01, % 99 had treatment-related effects, % 51 severe (grade 3). Common any-grade effects were nausea (% 77), alopecia/hair loss (% 48), fatigue (% 48), vomiting (% 45), constipation (% 34), decreased neutrophil count (% 31), reduced appetite (% 29), diarrhea (% 27), and anemia (% 26). Severe grade 3 and 4 effects were low neutrophils in% 31, nausea (% 7.6), and anemia (% 26). Severe lung toxicity occurred in 3 patients and was managed with cortisone.

Enhertu's dose recommendation was 5.4mg/kg. 

Below Are HER2-Targeted Breast Cancer Treatments. Enhertu (trastuzumab deruxtecan) Appears in Section “b”.

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