WASHINGTON -- The FDA of fam-trastuzumab deruxtecan (Enhertu) on Friday for the later-line treatment of unresectable or metastatic HER2-positive breast cancer.
The antibody-drug conjugate is indicated for patients who have received at least two prior anti-HER2-based regimens for their metastatic disease.
FDA's decision was based on results from the DESTINY-Breast01 trial, a single-arm trial of 184 women that demonstrated a response rate of 60.3% with the agent, including complete responses in 6%. The median duration of response was 14.8 months.
According to data presented at the San Antonio Breast Cancer Symposium earlier this month, median overall survival in the study was not reached. An estimated 93.9% of patients remained alive at 6 months and 86.2% remained alive at 1 year.
Participants in the trial had a median of six prior systemic therapies (range of two to 17), with all having already received trastuzumab (Herceptin) and T-DM1 (ado-trastuzumab emtansine; Kadcyla). Another 65% had received pertuzumab (Perjeta), 54% had some other anti-HER2 agent, and 99.5% had received some other systemic anti-cancer therapy.
Fam-trastuzumab deruxtecan has three key components: an anti-HER2 monoclonal antibody with the same amino acid as trastuzumab, a topoisomerase I inhibitor payload, and a tetra-peptide-based cleavable linker.
Labeling for the agent includes a boxed warning due to the risk of interstitial lung disease (ILD) and embryo-fetal toxicity. While women with a significant history of ILD were excluded from DESTINY-Breast01, ILD still proved to be an issue, leading to four ILD-related deaths and treatment cessation in five patients.
If symptoms of ILD occur, patients should undergo dose reductions, treatment breaks, or discontinue the drug, the FDA said.
Low-grade hematologic and gastrointestinal adverse events (AEs) were the main source of treatment-related toxicity in the trial. The most common grade 3 AEs were decreased neutrophil count (20.7%), anemia (8.7%), and nausea (7.6%).