Adjuvant Durvalumab Strategy in Locally Advanced Esophageal GEJ Adenocarcinoma

Hirva Mamdani, MD, an assistant professor of Medical Oncology, at the Karmanos Cancer Center, explains the rationale for conducting a safety and efficacy study of durvalumab (Imfinzi) in patients following multimodality therapy for locally advanced esophageal (LA-EAC) and gastroesophageal junction (GEJ) adenocarcinoma. Mamdani presented the 2-year follow-up data from this Big Ten Research Consortium study at the 2020 American Society of Oncology (ASCO) Gastrointestinal Cancers Symposium.

LA-EAC and GEJ adenocarcinoma are rising cancers in the United States, and disease progresses rapidly. Most patients already have locally advanced disease by the time they present to a medical oncologist. For patents who are considered medically fit, 1 of the standards of care is concurrent chemoradiation followed by surgery. However, 50% of these patients relapse within 1 year following treatment. The risk is of relapse is increased in patients who did not achieve a pathologic complete response with neoadjuvant treatment and those who had resistant disease in the lymph nodes at the time surgery. Because no adjuvant therapies have shown promise in these patients, the is an urgent unmet medical need to develop novel treatments.

One strategy for providing adjuvant treatment to patients with GEJ adenocarcinoma may be to administer immune checkpoint inhibitors. When directed at the PD-1/PD-L1 pathway, immune checkpoint inhibitors have shown activity in metastatic LA-EAC. The pathway is also upregulated in response to chemoradiation and chemotherapy. Based on these data, a study was conducted to determine whether adjuvant durvalumab, a PD-L1 inhibitor, following trimodal therapy, could reduce the risk of disease relapse in patients with GEJ.