Adjuvant Durvalumab Following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma

Abstract

Background: Concurrent chemoradiation (CRT) followed by esophagectomy is a standard of care for resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma. The relapse rate is high among patients who do not achieve a pathologic complete response (pCR) following neoadjuvant CRT. Methods: We conducted a phase II study of durvalumab in patients with locally advanced esophageal and GEJ adenocarcinoma who have undergone preoperative CRT followed by R0 resection with histologic evidence of persistent residual disease in the surgical specimen. Patients received durvalumab 1500 mg IV every four weeks for up to one year. The primary endpoint was 1-year relapse free survival (RFS).

Findings: Thirty-seven patients were enrolled. The majority (64∙9%) had pathologically positive lymph nodes. One-year RFS was 73%, and median RFS was 21 months (95% CI, 14-40.4 months). Nineteen (51∙4%) patients had PD-L1 CPS of ≥1% and 7 (18∙9%) had PD-L1 CPS of ≥10%. There was a numerical trend toward superior 1-year RFS among patients with PD-L1 positive disease compared to those with PD-L1 negative disease, using CPS of ≥10% (100% vs 66.7%, p=0.1551) and ≥1% (84.2% vs 61.1%, p=0.1510) cutoffs. The most common treatment related adverse events were fatigue (27%), diarrhea (18.9%), arthralgia (16.2%), nausea (16.2%), pruritus (16.2%), cough (10.8%), and increase in AST/ALT/bilirubin (10.8%). Three (8.1%) patients developed grade 3 immune mediated adverse events, including pneumonitis(1), colitis(1), and hepatitis(1).

Interpretation: Adjuvant durvalumab in patients with residual disease in the surgical specimen following trimodality therapy for locally advanced esophageal and GEJ adenocarcinoma led to clinically meaningful improvement in 1-year RFS compared to historical control rate. Higher PD-L1 expression may have a correlation with the efficacy of durvalumab in this setting.