Dr Eads on the Rationale for ECOG-ACRIN EA2174 in Esophageal/GEJ Adenocarcinoma

Jennifer R. Eads, MD, physician lead, GI Cancer Research, director, National Clinical Trials Network, Abramson Cancer Center, University of Pennsylvania, associate professor, clinical medicine (hematology-oncology), Penn Medicine, Perelman Center for Advanced Medicine, discusses the rationale for launching the phase 2/3 ECOG-ACRIN EA2174 trial (NCT03604991). The investigation evaluated adding nivolumab (Opdivo) to neoadjuvant chemotherapy and radiation in patients with locoregional esophageal and gastroesophageal junction (GEJ) adenocarcinoma.

The rationale for adding an immune checkpoint inhibitor to standard neoadjuvant chemotherapy and radiation in patients with esophageal adenocarcinoma stems from the poor prognosis associated with this disease, Eads begins. Currently, the standard treatment for localized esophageal or GEJ adenocarcinoma involves a combination of chemotherapy with carboplatin and paclitaxel, along with radiation therapy, followed by surgical resection, according to Eads. If residual disease is found during surgery, adjuvant nivolumab is administered, she says, notingthat this addition of adjuvant immunotherapy has improved outcomes for patients.

In the neoadjuvant setting, despite various trials exploring different treatment strategies, the pathologic complete response (pCR) rate has remained between 25% and 30%, Eads continues. Adding novel agents or additional chemotherapy has not significantly improved these outcomes, she says. Historically, pCR has been considered a marker for predicting long-term survival, so improving this rate has long been a major goal of treating patients with esophageal adenocarcinoma, she explains. Achieving a better pCR rate typically requires a treatment approach that combines both chemotherapy and radiation, Eads notes.

Immune checkpoint inhibitors have already demonstrated efficacy in the metastatic setting for patients with esophageal and GEJ adenocarcinoma, she continues. This success led to the logical question of whether these agents could also be beneficial in the neoadjuvant setting, she says. The hypothesis behind this approach is that radiation therapy may enhance the tumor’s immunogenicity, making it more responsive to immune checkpoint inhibition, Eads reports. By adding an immune checkpoint inhibitor to standard neoadjuvant regimens, the hope is to improve response rates, increase pCR, and ultimately enhance long-term survival outcomes for patients with this challenging disease, she concludes.