The FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu®, Daiichi Sankyo) for the treatment of adult patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive gastric or gastroesophageal adenocarcinoma previously treated with a trastuzumab-based regimen.
Approval was based on DESTINY-Gastric01 (NCT03329690), a multicenter, open-label, randomized trial. For this study, led by study author Kohei Shitara, MD, Chief of the Department of Gastrointestinal Oncology at the National Cancer Center Hospital East in Kashiwa, Japan, 187 patients with HER2-positive advanced gastric cancer were enrolled. To be eligible, patients were required to have centrally confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma that progressed after at least two prior therapies, including trastuzumab. In a 2:1 ratio, patients received either fam-trastuzumab deruxtecan-nxki, at a dose of 6.4 mg per kg of body weight every 3 weeks, or physician's choice of chemotherapy.
Objective response was significantly higher in the treatment arm compared with the physician's choice group (51% vs 14%), as was median overall survival (12.5 vs 8.4 months) and median progression-free survival (5.6 vs 3.5 months). The median duration of response was 11.3 months in the treatment arm, compared with 3.9 months in the control group.
The most common treatment-related adverse events, occurring in at least 20% of patients, included anemia, leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, nausea, decreased appetite, increased aspartate aminotransferase, fatigue, increased blood alkaline phosphatase, increased alanine aminotransferase, diarrhea, hypokalemia, vomiting, constipation, increased blood bilirubin, pyrexia, and alopecia. The prescribing information includes a warning regarding the risks of interstitial lung disease and embryo-fetal toxicity.
"Overall, treatment with [fam-trastuzumab deruxtecan-nxki] led to a significantly higher percentage of patients with an objective response and to longer overall survival than conventional chemotherapy among patients with HER2-positive, advanced gastric or gastroesophageal junction cancer. Antitumor activity was noted in patients who had disease progression while they had been receiving regimens including trastuzumab. Noteworthy toxic effects included myelosuppression and interstitial lung disease, which was ameliorated by dose reductions and interruptions," concluded Dr. Shitara and colleagues in their June publication of the trial results in The New England Journal of Medicine.
The recommended dose for fam-trastuzumab deruxtecan-nxki for patients with gastric cancer is 6.4 mg/kg, administered intravenously once every 21 days until disease progression or unacceptable toxicity.
For More Information
US Food & Drug Administration (2020). FDA approves fam-trastuzumab deruxtecan-nxki for HER2-positive gastric adenocarcinomas. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-fam-trastuzumab-deruxtecan-nxki-her2-positive-gastric-adenocarcinomas
Image Courtesy of Calicut Medical College. Licensed under CC BY-SA 4.0