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ESMO 2025 | The potential role of T-Dxd in the first-line setting for HER2+ unresectable/metastatic GC/GEJA
Filippo Pietrantonio, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, discusses the potential role of trastuzumab deruxtecan (T-DXd) in the first-line setting, highlighting its high single-agent activity in gastric cancer and the rationale for combining it with other therapies, such as chemotherapy and immune checkpoint inhibitors. Dr Pietrantonio notes that studies like the Phase III DESTINY-Gastric04 (NCT04704934) have shown that T-DXd can be safely combined with fluoropyrimidines and immunotherapy, and ongoing Phase III studies are investigating T-DXd-based combinations in the first-line setting. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
Trastuzumab deruxtecan has the highest single agent activity in gastric cancer so the overall response rate is between 40 to 50 percent so there is a strong rationale to bring this agent to the first line setting of course in combination so we know that chemotherapy plus immune checkpoint inhibitors and trastuzumab is a standard of care based on the Keynote 811 study results so of course there is a rationale to study the safety and the preliminary efficacy of several trastuzumab deruxtecan combinations in the first line setting and for instance the DGO3 study was a phase 1b study conducted also in the first line setting and investigating several combinations...
Trastuzumab deruxtecan has the highest single agent activity in gastric cancer so the overall response rate is between 40 to 50 percent so there is a strong rationale to bring this agent to the first line setting of course in combination so we know that chemotherapy plus immune checkpoint inhibitors and trastuzumab is a standard of care based on the Keynote 811 study results so of course there is a rationale to study the safety and the preliminary efficacy of several trastuzumab deruxtecan combinations in the first line setting and for instance the DGO3 study was a phase 1b study conducted also in the first line setting and investigating several combinations. So based on this study’s results several patients were enrolled in this study globally and the key message of this study is that trastuzumab deruxtecan can be safely combined with a fluoropyrimidine and also with immunotherapy. So basically now the ongoing phase three studies, the preliminary results were also good for the DGO3 study. So now the ongoing phase three studies in the first-line setting are investigating T-DXd plus a fluoropyrimidine and pembrolizumab versus standard of care, KEYNOTE-811 regimen in the first line setting in HER2 positive disease. Or there are other Phase III studies also adding other immune checkpoint inhibitors to these T-DXd based experimental combinations in the first line, such as the anti-PD-1 and TIGIT monoclonal antibody, so we will see, these trials are ongoing, we will see whether we will be able to move the use of trastuzumab deruxtecan in the first line setting as part of a combination regimen.
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