The Food and Drug Administration (FDA) has approved Enhertu® (fam-trastuzumab deruxtecan-nxki; Daiichi Sankyo and AstraZeneca) for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.
The approval was based on data from the phase 2 DESTINY-Gastric01 trial, which included 188 patients with HER2-positive, locally advanced or metastatic gastric or GEJ adenocarcinoma who had progressed on at least 2 prior regimens including trastuzumab, a fluoropyrimidine- and a platinum-containing chemotherapy. Patients were randomized to receive fam-trastuzumab deruxtecan-nxki 6.4mk/kg intravenously every 3 weeks (n=128) or physician’s choice of monotherapy with irinotecan (n=55) or paclitaxel (n=7).
Results showed overall survival was 12.5 months (95% CI, 9.6-14.3) in the fam-trastuzumab deruxtecan-nxki 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). Among patients treated with fam-trastuzumab deruxtecan-nxki, the objective response rate was 40.5% (95% CI, 31.8-49.6) vs 11.3% (95% CI, 4.7-21.9) for those receiving irinotecan or paclitaxel.
Median progression free survival was observed to be 5.6 months (95% CI, 4.3-6.9) in the fam-trastuzumab deruxtecan-nxki arm compared with 3.5 months (95% CI, 2.0-4.3) in the irinotecan or paclitaxel arm; median duration of response was found to be 11.3 months (95% CI, 5.6, NR) and 3.9 months (95% CI, 3.0-4.9), respectively.
“Today’s approval of Enhertu represents the first HER2 directed medicine approved in a decade for patients with HER2 positive metastatic gastric cancer,” said Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca. “The results from the DESTINY-Gastric01 trial highlight the potential to change clinical practice, showing a 41% improvement in survival and a response rate more than 3 times higher with Enhertu compared to chemotherapy.”
The most common adverse reactions observed in the DESTINY-Gastric01 trial with fam-trastuzumab deruxtecan-nxki 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.
In addition to the gastric cancer indication, Enhertu is also indicated for unresectable or metastatic HER2-positive breast cancer in patients who have received 2 or more prior anti-HER2-based regimens in the metastatic setting.
FDA approves fam-trastuzumab deruxtecan-nxki for HER2-positive gastric adenocarcinomas. [press release]. Silver Spring, MD: US Food and Drug Administration; January 15, 2021.