EA2183: A phase III study of consolidative radiotherapy in patients with oligometastatic HER2-negative esophageal and gastric adenocarcinoma.

TPS4162 Background: Advanced esophageal and gastric adenocarcinomas (EGA) have poor prognosis. Doublet chemotherapy with fluoropyrimidine and platinum agents in combination with nivolumab for PD-L1 positive tumors is now the standard first-line approach, but overall survival (OS) remains < 1.5 years. A subset of EGA patients have limited burden of metastatic disease. There is accumulating evidence that patients with oligometastatic states across disease types may benefit from locoregional ablative therapies during the course of their treatment. EA2183 is the first prospective study to evaluate the potential benefits of consolidative radiotherapy (XRT) in oligometastatic EGA. Methods: This is a prospective, randomized phase 3 study evaluating the role of consolidative XRT in oligometastatic EGA. Patients with ≤3 metastases at the time of diagnosis of advanced disease are eligible for enrollment. After completion of 4 months of systemic therapy, patients whose disease has not progressed are randomized to consolidation with XRT to all sites of disease followed by continuation of systemic therapy or continuation of systemic therapy alone. Patients are able to enroll in the study at the time of diagnosis of advanced disease or after completion of induction therapy. Systemic therapy is left to the discretion of the treating physician and can include FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine, oxaliplatin) in combination with nivolumab. Unless there are contraindications to immunotherapy or a history of prior treatment with immune checkpoint inhibitors, nivolumab use is mandatory if tumor has PD-L1 combined positive score (CPS) ≥5. The goal of radiation is to consolidate gains made by chemotherapy by delivering the highest dose that maintains the greatest tumor control probability that is also safe to deliver given the anatomic and normal tissue constraints. Specific radiation dose and fractionation are recommended in the protocol but is left to the discretion of the treating radiation oncologist to choose the course that is most suitable. Radiation must be administered over a maximum of 15 treatment days to minimize systemic therapy treatment breaks. Primary endpoint is OS from the time of randomization. Secondary endpoints include progression free survival from the time of randomization and safety and tolerability of consolidative XRT. We hypothesize that consolidative XRT will prolong OS from 10 to 15.6 months (an increase in median OS of 55.6%). The study is planning to enroll 314 patients with the goal of randomizing 204 patients in a 2:1 fashion. Stratification factors include number of metastatic sites, choice of immunotherapy with relation to PD-L1 CPS, as well as time of registration to the protocol (before or after systemic therapy initiation). Enrollment to the study is ongoing. Clinical trial information: NCT04248452.