Targeted Therapy Options for Gastric/GEJ Cancers Expand
Ronan J. Kelly, MD, MBA, discusses the targeted therapy options that have become available for patients with gastric, esophageal, and gastroesophageal junction cancers.
Ronan J. Kelly, MD, MBA, director of oncology at the Charles A. Sammons Cancer Center at Baylor University Medical Center in Dallas, Texas, and the chief of oncology for the Baylor, Scott, and White Health System in North Texas, discusses the targeted therapy options that have become available for patients with gastric, esophageal, and gastroesophageal junction (GEJ) cancers.
Oncologists have been waiting for more targeted therapies to enter the gastric/GEJ cancer landscape, Kelly says. Previously, HER2 was the only available target; now, immune checkpoint inhibitors nivolumab (Opdivo), ipilimumab (Yervoy), and pembrolizumab (Keytruda) can be used in this setting. Another targeted drug, zolbetuximab (Vyloy), is an anti–Claudin 18.2 antibody that was approved in 2024.
Kelly also points to improvements in HER2 targeting with trastuzumab (Herceptin) being used in combination with chemotherapy and pembrolizumab in the first line of treatment and trastuzumab deruxtecan (Enhertu) being used in subsequent lines for recurrent disease. Finally, for patients with microsatellite instability (MSI) high/mismatch repair deficient (dMMR) tumors independently of PD-L1 status, immune checkpoint inhibitors can be used alone.
For this reason, Kelly says that the standard-o- care testing before treatment in the first-line metastatic setting should cover HER2 expression, PD-L1 combined positive score (CPS), Claudin 18.2 expression, and MSI-high/dMMR status.
TRANSCRIPTION
0:10 | We've been waiting for many years for personalized medicine to come into gastric and GEJ cancers, because for many years, we just had the ability to target HER2. But now, in the last number of years, as you know, the immune checkpoint inhibitors have really entered in a lot of solid tumors, especially also in gastric and GEJ as well as esophageal cancer. We do have the immune checkpoint inhibitors approved just in the last number of months, a new drug called zolbetuximab, which targets Claudin 18.2. It has also been approved, which is an exciting development.
0:52 | And in addition to that, we already have HER2 which we've been hopefully adding incremental benefits in terms of novel HER- targeted agents, and we've seen the combination of an immune checkpoint inhibitor plus chemotherapy plus trastuzumab becoming first line now in those [who] are PD-L1 positive, so that was a big advance. The dMMR, MSI-high tumors, we also want to make sure we don't miss those.
1:28 | So really now, standard of care across gastric and GEJ cancers in the first-line metastatic setting is making sure we check for HER2 expression, PD-L1 measured by CPS, Claudin 18.2, and MSI-high or dMMR.
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