FDA Approves Fam-Trastuzumab Deruxtecan-nxki for HER2+ Gastric Adenocarcinomas

The FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of patients with locally advanced or metastatic HER2-postive gastric or gastroesophageal (GEJ) adenocarcinoma who previously received a trastuzumab-based regimen, according to the agency.

The FDA based its approval on findings from the multicenter, open-label, randomized DESTINY-Gastric01 trial (NCT03329690), which involved 188 patients with metastatic gastric or GEJ adenocarcinoma who progressed on at least 2 prior regimens: trastuzumab, a fluoropyrimidine-, or a platinum-containing chemotherapy. Participants were randomized 2:1 to receive either 6.4 mg/kg of fam-trastuzumab deruxtecan-nxki every 3 weeks or physician’s choice of either irinotecan or paclitaxel.

Overall survival (OS), a co-primary end point, was higher in the fam-trastuzumab deruxtecan-nxki arm compared with the physician’s choice arm (12.5 months vs. 8.4 months, respectively.) Fam-trastuzumab deruxtecan-nxki also bested physician’s choice in objective response rate (ORR), the other co-primary end point. Confirmed ORR was 40.5% in the fam-trastuzumab deruxtecan-nxki arm, compared with 11.3% in the irinotecan or paclitaxel monotherapy arms.

Average progression-free survival (PFS) was also better with the fam-trastuzumab deruxtecan-nxki arm, at 5.6 months, compared to 3.5 months in the physicians’ choice arm. Average duration of response was 11.3 months in the experimental arm, compared with 3.9 months in the physcians’ choice arm.

Common adverse events, including laboratory abnormalities, that occurred in 20% or more of patients 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.

Nurses and other providers should note that the prescribing information for fam-trastuzumab deruxtecan-nxki includes a boxed warning regarding interstitial lung disease and embryo-fetal toxicity.