Trastuzumab deruxtecan for gastric cancer: HTA assessment of considerable added benefit

Based on a comparative study initiated by the manufacturer prior to marketing authorization, IQWiG now sees a considerable added benefit of treatment with trastuzumab deruxtecan for patients with advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma.

The example of the DESTINY-Gastric04 study conducted in parallel with the marketing authorization for trastuzumab for gastric cancer demonstrates that it is both possible and necessary to plan and initiate 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.

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.