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FDA Approves Fam-Trastuzumab Deruxtecan-nxki for Previously Treated Patients With HER2-Positive Gastric Cancers


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On January 15, the U.S. Food and Drug Administration (FDA) approved fam-trastuzumab deruxtecan-nxki (Enhertu) for adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.

DESTINY-Gastric01

Efficacy was evaluated in the multicenter, open-label, randomized DESTINY-Gastric01 trial in patients with HER2-positive locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma who had disease progression on at least two prior regimens, including trastuzumab, a fluoropyrimidine-, and a platinum-containing chemotherapy. A total of 188 patients were randomly assigned 2:1 to receive trastuzumab deruxtecan at 6.4 mg/kg intravenously every 3 weeks or physician’s choice of either irinotecan or paclitaxel monotherapy.

The main efficacy outcome measures were overall survival and objective response rate assessed by independent central review (Response Evaluation Criteria in Solid Tumors version 1.1) in the intent-to-treat population. Additional efficacy outcome measures were progression-free survival and duration of response.

Overall survival was 12.5 months (95% confidence interval [CI] = 9.6–14.3) in the trastuzumab deruxtecan arm compared with 8.4 months (95% CI = 6.9–10.7) in the irinotecan or paclitaxel arm (hazard ratio [HR] = 0.59, 95% CI = 0.39–0.88, P = .0097). Confirmed objective response rate was 40.5% (95% CI = 31.8%–49.6%) in the trastuzumab deruxtecan arm compared with 11.3% (95% CI = 4.7%–21.9%) for those receiving irinotecan or paclitaxel. Median progression-free survival was 5.6 months (95% CI = 4.3–6.9) in the trastuzumab deruxtecan arm compared to 3.5 months (95% CI = 2.0–4.3) in the irinotecan or paclitaxel arm. Median duration of response was 11.3 months (95% CI = 5.6–not reached) vs 3.9 months (95% CI = 3.0–4.9), respectively.

The most common (≥ 20%) adverse reactions including laboratory abnormalities were 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 boxed warning to advise health professionals of the risks of interstitial lung disease and embryofetal toxicity.

The recommended dose of trastuzumab deruxtecan for gastric cancer is 6.4 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.


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