Dr. Uboha (University of Wisconsin/UW Carbone Cancer Center) is the study chair for this trial. The study co-chairs are Lakshmi Rajdev, MD, MS (Lenox Hill Hospital/Northwell Health Cancer Institute), Michael Gibson, MD, PhD (Vanderbilt University/Ingram Cancer Center), and George Fisher, MD (Stanford University/Stanford Cancer Institute).
NCTN Group Study Champions: Jon Strasser, MD for Alliance (Christiana Care Health System) and Kimberley Mak, MD, MPH (Boston University/Boston Medical Center) for NRG Oncology.
Esophageal and gastric cancers are a major health problem worldwide. In Western countries, lower gastroesophageal adenocarcinoma, which frequently involves the gastroesophageal junction, is the most common primary site and histological subtype of upper gastrointestinal tumors. The incidence of these cancers in both male and female patients is on the rise, including increases in patients under the age of 50, who are commonly diagnosed in advanced stages. Stage IV disease is almost universally fatal, with 5-year survival rates of less than 5%. Systemic therapy plays a critical role in managing metastatic esophageal and gastric adenocarcinoma (EGA). Doublet fluoropyrimidine and platinum-based chemotherapy, in combination with nivolumab for PD-L1-positive tumors, is now a standard first-line approach.
A subset of EGA patients have limited burden of metastatic disease, and at least some of these patients may be undertreated with current strategies. Aggressive treatment of oligometastatic disease can significantly extend survival in a number of tumor types. Increased interest in oligometastatic status has been fueled both by the development of highly effective noninvasive ablation approaches, as well as improvements in systemic therapy. There are no standard treatments or classifications of oligometastatic EGA. Nevertheless, multiple literature reports suggest that a subset of patients with EGA who have a limited burden of metastatic disease may benefit from more aggressive management. EA2183 is the first prospective study to evaluate the potential benefits of locoregional debulking with radiotherapy (XRT) in oligometastatic EGA and to define oligometastatic EGA.
EA2183 is a randomized phase III study evaluating the role of consolidative radiotherapy (XRT) in oligometastatic EGA. For this study, oligometastatic state is defined by the presence of ≤3 metastases at the time of diagnosis of advanced disease. After completing 4 months of systemic therapy, patients whose disease has not progressed are randomized to consolidation with either XRT to all sites of disease followed by continuation of systemic therapy or continuation of systemic therapy alone. Patients may enroll in the study at the time of diagnosis of advanced disease or after completion of induction therapy.
The treating physician will choose the systemic therapy, which can include FOLFOX or CAPOX chemotherapy in combination with nivolumab. Nivolumab is mandatory if the tumor has a PD-L1 combined positive score (CPS) ≥5 unless there are contraindications to immunotherapy or a history of prior treatment with immune checkpoint inhibitors in early-stage disease. Radiation therapy is administered over a maximum of 15 treatment days to minimize systemic therapy treatment breaks.
The primary endpoint of this study is overall survival from the time of randomization. Secondary endpoints include progression-free survival from the time of randomization and the safety and tolerability of consolidative XRT. We hypothesize that consolidative XRT will prolong overall survival (OS) from 10 months in the control group to 15.6 months with a manageable toxicity profile. The study plans to enroll 314 patients and randomize 204 patients 2:1 to radiation versus standard therapy.
EA2813 is an instrumental study that has the potential to prolong OS and change the standard of care in a subset of patients with EGA. Enrollment to this study is ongoing.
Learn more about the EA2183 trial at ecog-acrin.org.