Dana-Farber Cancer InstituteNew Targeted Treatments Emerge for Gastric and Esophageal Cancer

Clinical trials have shown the benefit of pembrolizumab (Keytruda®) in combination with standard chemotherapy for advanced esophageal cancer and Siewert type 1 gastro-esophageal junction cancer, significantly improving survival.

Advanced forms of gastric and esophageal cancer have historically had limited treatment options, predominantly chemotherapy. Recent clinical trials, however, have revealed the effectiveness of targeted therapies, including immunotherapies and antibodies targeting specific proteins, in significantly improving survival and adding diversity to the standard of care.

Key Points:

• Another immunotherapy drug, nivolumab, has proven effective in several settings including as first-line and adjuvant therapy.
• Therapies targeting HER2, such as trastuzumab and trastuzumab deruxtecan (T-DXd), have become crucial in treating some gastric and esophageal tumors.
• An FGFR2B-blocking antibody, bemarituzumab, in combination with FOLFOX, shows promise for FGFR2B-positive tumors, with a phase 3 study ongoing.
• The SPOTLIGHT trial demonstrated the effectiveness of zolbetuximab, an antibody blocking the CLDN18.2 protein, in improving overall survival by roughly two months.

Additional Points:

• The principal investigator of the KEYNOTE-590 trial, Peter Enzinger, MD, highlights the rapidly evolving therapeutic landscape of these cancers.
• Enzinger’s research also includes exploring the effectiveness of CLDN18.2-targeting therapies, recognizing their potential despite a modest survival benefit.

Conclusion:

• The introduction of these targeted treatments represents a substantial advancement in gastric and esophageal cancer care, moving away from the traditional one-size-fits-all chemotherapy approach to more tailored, effective options.

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