How Immunotherapy Is Changing Esophageal Cancer Treatment

The Role of Pembrolizumab and Nivolumab in Mismatch Repair Deficiency

Pembrolizumab (Keytruda®) and nivolumab (Opdivo®) are the primary immunotherapy drugs used to treat esophageal cancers with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status. These drugs target the PD-1/PD-L1 pathway to enhance immune responses against cancer cells.

Key details:

  • Pembrolizumab is FDA-approved for dMMR/MSI-H solid tumors, including esophageal and gastroesophageal junction (GEJ) cancers. It is administered intravenously every 3 or 6 weeks.

  • Nivolumab is also used for dMMR esophageal or GEJ cancers, particularly after chemotherapy and radiation. It is typically given every 2–4 weeks.

Clinical trials have shown both drugs improve outcomes in dMMR/MSI-H gastrointestinal cancers, with pembrolizumab specifically approved for broader dMMR tumor applications. For example, in the KEYNOTE-059 trial, pembrolizumab demonstrated efficacy in PD-L1–positive GEJ adenocarcinomas. Nivolumab’s approval followed trials like CheckMate-142, which highlighted its activity in MSI-H colorectal cancer, with implications for esophageal cases.

These therapies are prioritized for advanced or metastatic cases where traditional treatments (surgery, chemoradiation) are ineffective.

References:

  1. https://www.cancer.org/cancer/types/esophagus-cancer/treating/immunotherapy.html

  2. https://www.cancerresearch.org/cancer-types/esophageal-cancer

  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC6409193/

  4. https://www.keytruda.com

  5. https://pmc.ncbi.nlm.nih.gov/articles/PMC10022879/

  6. https://www.sciencedirect.com/science/article/pii/S0003497524001255

  7. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21813

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