Japan’s PMDA has approved an update to the prescribing information of Enhertu, expanding its use to include second-line treatment of patients with HER2-positive unresectable advanced or recurrent gastric cancer. The decision follows a review of results from the DESTINY-Gastric04 phase III trial and marks a significant shift from its earlier approval as a third-line therapy.

Developed by Daiichi Sankyo, Enhertu is a HER2-directed antibody-drug conjugate designed to target tumour cells with high precision. The expanded indication addresses a major unmet need, as no HER2-targeted therapy had previously demonstrated a survival benefit in the second-line metastatic setting.

Gastric cancer remains a major health burden in Japan, with over 125,000 new cases and more than 43,000 deaths reported in 2022. Approximately 20 percent of these cases are HER2-positive, a subtype associated with aggressive disease progression.

Data from the DESTINY-Gastric04 trial showed that Enhertu reduced the risk of death by 30 percent compared to the standard treatment combination of ramucirumab and paclitaxel. Median overall survival improved to 14.7 months in patients treated with Enhertu, compared to 11.4 months in the comparator group. The findings were presented at the 2025 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine.

The safety profile of Enhertu in the trial was consistent with previous studies, with commonly reported adverse effects including fatigue, decreased neutrophil count, nausea and anaemia. However, the drug carries a warning for Interstitial Lung Disease (ILD), a potentially serious condition observed in clinical trials, necessitating close monitoring during treatment.

DESTINY-Gastric04 enrolled 494 patients globally and evaluated the efficacy and safety of Enhertu against standard therapy in patients whose disease had progressed following trastuzumab-based treatment.

Enhertu is part of a broader oncology pipeline leveraging Daiichi Sankyo’s proprietary DXd antibody-drug conjugate technology. The drug is already approved in multiple countries for various HER2-targeted indications, including breast and lung cancers and continues to be studied across several tumour types in global clinical trials.

The regulatory update reinforces Enhertu’s role as a key treatment option in HER2-positive cancers and underscores ongoing progress in targeted cancer therapies.