Integrating Nivolumab into Esophageal/Gastroesophageal Junction Cancer Treatment

Strategic Insights -

Ronan J. Kelly, MD, MBA, discussed the integration of nivolumab (Opdivo) following chemoradiation in patients with esophageal/gastroesophageal junction (GEJ) cancers at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Kelly, director of Oncology at the Charles A. Sammons Cancer Center and W.W. Caruth Jr., Endowed Chair of Immunology at Baylor University Medical Center, emphasized the importance of considering perioperative treatment with the MATTERHORN regimen, which has shown to be the better option for patients with gastric and GEJ cancers. He also highlighted the potential role of radiation in treating esophageal squamous cell carcinoma and the benefits of adjuvant nivolumab in improving overall survival.

Key Takeaways:

  • The phase 3 CheckMate 577 study demonstrated a 19-month improvement in overall survival for patients with esophageal squamous cell carcinoma who received chemoradiation and surgery followed by nivolumab.
  • The MATTERHORN trial evaluating the addition of durvalumab (Imfinzi) to fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) in resectable gastric/gastroesophageal junction cancer showed benefits over FLOT alone.
  • A decrease in the use of neoadjuvant chemoradiation in gastric and GEJ cancers may lead to the adoption of perioperative treatment with the MATTERHORN regimen.
  • Radiation still has a role to play in treating esophageal squamous cell carcinoma.
  • In younger, fitter patients with esophageal adenocarcinoma, the perioperative FLOT regimen may become the new standard of care.
  • Clinicians may prefer chemoradiation/nivolumab in the elderly and frailer population due to their intolerance to surgery.
  • The choice between chemoradiation/nivolumab and perioperative FLOT will depend on the individual patient's tolerance and suitability for each treatment.
  • A key consideration is avoiding treatment that may lead to frailty or sickness, making subsequent surgery challenging.

Statistics:

  • 19 months: improvement in overall survival for patients with esophageal squamous cell carcinoma who received chemoradiation and surgery followed by nivolumab in the CheckMate 577 study.
  • Ongoing: phase 3 CheckMate 577 study evaluating the efficacy of adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer.
  • Unapproved: status of the MATTERHORN trial (NCT04592913) evaluating the addition of durvalumab to FLOT in resectable gastric/gastroesophageal junction cancer.

Sources:

1. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): first results of overall survival (OS) from CheckMate 577. J Clin Oncol. 2025;43(suppl 16):4000. doi:10.1200/JCO.2025.43.16_suppl.4000

2. Janjigian Y, Al-Batran S-E, Wainberg Z, et al. Event-free survival (EFS) in MATTERHORN: a randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC). J Clin Oncol. 2025;43(suppl 16):4000. doi:10.1200/JCO.2025.43.17_suppl.LBA5