Immunotherapy for Resectable Locally Advanced Esophageal Carcinoma

ABSTRACT

BACKGROUND

The current standard of care for locally advanced esophageal and gastroesophageal junction (GEJ) cancers includes either neoadjuvant chemoradiotherapy or perioperative chemotherapy with surgery; however, disease-free survival in these patients remains poor. Immune checkpoint inhibitors (ICIs) are approved for adjuvant treatment of locally advanced esophageal and GEJ cancers, but their benefit in the perioperative and neoadjuvant settings remains under investigation.

METHODS

We conducted a literature search to identify studies that investigated immunotherapy for locally advanced esophageal and GEJ carcinoma using the PubMed online database. A review of ClinicalTrials.gov yielded a list of ongoing trials.

RESULTS

Adjuvant nivolumab for residual disease following neoadjuvant chemoradiotherapy and surgery is the only approved immunotherapy regimen for locally advanced esophageal cancer. Early phase trials investigating the addition of neoadjuvant or perioperative ICIs to standard-of-care multimodality approaches have observed pathologic complete response rates as high as 60%. Response rates are highest for ICIs plus chemoradiotherapy for esophageal squamous cell carcinoma and dual checkpoint inhibition in mismatch repair deficient adenocarcinomas. Safety profiles are acceptable, with a pooled adverse event rate of 27%. Surgical morbidity and mortality with immunotherapy are similar to historical controls (no immunotherapy), and R0 resection rates are high. When reported, disease-free survival among patients treated with perioperative immunotherapy is promising.

CONCLUSIONS

Outside of clinical trials, immunotherapy for resectable esophageal carcinoma is limited to the adjuvant setting. Phase III trials investigating neoadjuvant and perioperative immunotherapy are now underway and will provide much-needed data on survival that may ultimately lead to practice-changing recommendations.