Enhertu Gets Tumor-Agnostic FDA Approval for HER2-Positive Cancers

The FDA granted tumor-agnostic accelerated approval to trastuzumab deruxtecan (Enhertu) for previously treated unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid cancers.

The action represents the first tumor-agnostic approval for an antibody-drug conjugate targeting HER2-positive tumors. According to an FDA statement, the approval had support from three clinical trials of patients with previously treated unresectable/metastatic HER2-positive (IHC3+) solid tumors: DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. DESTINY-PanTumor02 involved patients with different types of solid tumors, whereas DESTINY-Lung01 enrolled patients with lung cancer and DESTINY-CRC02 patients with colorectal cancer.

Collectively, the studies enrolled a total of 192 adults. The primary outcome for all three trials was confirmed objective response rate (ORR). Median duration of response (DOR) also was evaluated. The results showed the following:

• DESTINY-PanTumor02: ORR 51.4%, DOR 19.4 months
• DESTINY-Lung02: ORR 52.9%, DOR 6.9 months
• DESTINY-CRC02: ORR 46.9%, DOR 5.5 months

Adverse events occurring in ≥20% of patients were decreased white blood cell count, nausea, decreased hemoglobin, decreased neutrophil count, fatigue, decreased lymphocyte count, decreased platelet count, increased liver function tests, increased blood alkaline phosphatase, vomiting, decreased appetite, alopecia, diarrhea, decreased blood potassium, constipation, decreased sodium, stomatitis, and upper respiratory tract infections. Labeling includes a boxed warning about a risk of interstitial lung disease and embryo-fetal toxicity.

Full approval for the indication may be contingent on verification of clinical benefit in confirmatory trials.

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