Nivolumab combination therapy as first-line treatments for unresectable, advanced or metastatic esophageal squamous cell carcinoma

Expert Rev Anticancer Ther. 2023 Jun;23(6):565-571. doi: 10.1080/14737140.2023.2207826. Epub 2023 May 8.


Introduction: Esophageal cancers continue to confer a dismal prognosis. Targeted and immune therapies have skyrocketed in the world of cancer management. Unlike other solid tumors, esophageal squamous cell carcinoma (ESCC) has lacked effective targeted therapy. Promising outcomes with immune checkpoint inhibitors (ICIs) have recently changed ESCC management.

Areas covered: Nivolumab has been granted several approvals to treat ESCC patients. Nivolumab is recommended as adjuvant therapy for localized ESCC patients following trimodality therapy who have residual cancer in the surgical specimen (lymph node(s) and or the primary). CheckMate-648 led to dual ICI therapy approval with nivolumab plus ipilimumab or nivolumab plus platinum with fluoropyrimidine as first-line treatment for unresectable ESCC patients. ATTRACTION-3 resulted in nivolumab approval for second-line therapy of unresectable ESCC patients who have not been exposed to ICI. Here we provide a review of nivolumab and how this relates to ESCC management.

Expert opinion: Some ESCC patients will not experience a response to ICIs. Determining intrinsic and acquired resistance patterns are needed to further capitalize on ICI therapy for ESCC patients. PD-L1 expression has been explored as a potential biomarker. Data show, however, PD-L1 positive tumor patients benefit but this assessment is not always needed.

Keywords: Checkpoint inhibitor; PD-1; PD-L1; gastroesophageal cancer; immunotherapy; nivolumab; pembrolizumab.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen
  • Esophageal Neoplasms*
  • Esophageal Squamous Cell Carcinoma*
  • Humans
  • Ipilimumab
  • Nivolumab


  • Nivolumab
  • B7-H1 Antigen
  • Ipilimumab