Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma.

Trastuzumab deruxtecan (Enhertu^®) is a human epidermal growth factor receptor type 2 (HER2)-directed antibody-drug conjugate that is approved in several countries globally for adults with advanced HER2-positive gastric or gastro-oesophageal junction (GOJ) adenocarcinoma who have received a prior trastuzumab-based regime. In the phase II DESTINY-Gastric01 trial, intravenous trastuzumab deruxtecan was significantly more effective than standard chemotherapy (physician's choice of intravenous irinotecan or paclitaxel) in achieving objective response and improving overall survival in Japanese or South Korean adults with advanced HER2-positive gastric or GOJ adenocarcinoma who had received two or more previous therapies. In the phase II DESTINY-Gastric02 trial, trastuzumab deruxtecan was able to induce durable response in adults from the USA or Europe with unresectable or metastatic HER2-positive gastric or GOJ adenocarcinoma. Trastuzumab deruxtecan was generally tolerable in these patients; the most common adverse events included nausea, neutropenia, fatigue and decreased appetite. Trastuzumab deruxtecan carries regulatory warnings (including boxed warnings in the USA) for interstitial lung disease/pneumonitis and embryo-foetal toxicity. Current evidence indicates that trastuzumab deruxtecan is an effective treatment option, and is generally tolerable, in previously treated adults with advanced HER2-positive gastric or GOJ adenocarcinoma.