Trastuzumab deruxtecan for gastric cancer: now a considerable added benefit

The antibody-drug conjugate trastuzumab deruxtecan holds a marketing authorization for several therapeutic indications, and is used for the treatment of various tumours (such as those in the breast or lung). In an early benefit assessment procedure, the Institute for Quality and Efficiency in Health Care (IQWiG) has now conducted a reassessment to determine whether trastuzumab deruxtecan offers an advantage versus the appropriate comparator therapy in adults with advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma who have already received a prior trastuzumab-based regimen as first-line treatment. Stomach cancer is called ‘HER2-positive’ when the tumour cells have a very large number of HER2 receptors to which growth factors bind, stimulating cell division.

Trastuzumab deruxtecan had already received marketing authorization for this therapeutic indication in December 2022. However, the subsequent early benefit assessment conclusion reached was ‘added benefit not proven’, as the manufacturer had not provided any suitable data. The manufacturer has now itself requested a further benefit assessment, based on new scientific findings. The basis for this was the DESTINY-Gastric04 study, which was initiated by the manufacturer prior to marketing authorization in May 2021 and compares treatment with trastuzumab deruxtecan with the current standard therapy of ramucirumab plus paclitaxel. Not only in terms of overall survival, but also with regard to side effects, the overall positive effects of trastuzumab deruxtecan clearly prevail; in summary, there is a hint of a considerable added benefit. This means that informative data is now available on whether trastuzumab deruxtecan offers an advantage versus the current standard of care.

Katrin Nink, Division Head at IQWiG’s Drug Assessment Department, highlights that the manufacturer launched a suitable study of direct comparison in parallel with the marketing authorization: “Time and again, we see that manufacturers’ study designs are primarily geared towards obtaining marketing authorization, leaving questions relating to the early benefit assessment unanswered. The example of the DESTINY-Gastric04 study shows that it is both possible and necessary to plan and initiate the necessary comparative studies versus the current standard of care even before a drug receives marketing authorization. The sooner, the better. To encourage this, appropriate incentives must also be included in any AMNOG reform."

Publication date original (German-language) report: 2 January 2026; English translation: July 2026

The G‑BA decides on the extent of the added benefit

The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the Federal Joint Committee (G-BA). After publication of the dossier assessment, the G‑BA conducts a commenting procedure and makes a decision on the extent of the added benefit.