Abstract

PURPOSE: The CROSS trial established neoadjuvant chemoradiotherapy (nCRT) for patients with resectable esophageal adenocarcinoma (rEAC). In the PERFECT trial we investigated the feasibility and efficacy of nCRT combined with programmed-death ligand-1 (PD-L1) inhibition for rEAC.

EXPERIMENTAL DESIGN: Patients with rEAC received nCRT according to the CROSS regimen combined with five cycles of atezolizumab (1200 mg). The primary endpoint was the feasibility of administering five cycles of atezolizumab in {greater than or equal to}75% patients. A propensity score-matched nCRT cohort was used to compare pathological response, overall survival and progression-free survival. Exploratory biomarker analysis was performed on repeated tumor biopsies.

RESULTS: We enrolled 40 patients of whom 85% received all cycles of atezolizumab. Immune related adverse events of any grade were observed in six patients. In total 83% proceeded to surgery. Reasons for not undergoing surgery were progression (n=4), patient choice (n=2) and death (n=1). The pathological complete response rate was 25% (10/40). No statistically significant difference in response or survival was found between the PERFECT and the nCRT cohort. Baseline expression of an established IFNy-signature was higher in responders compared to non-responders (p=0.043). On-treatment non-responders showed either a high number of cytotoxic lymphocytes (CTLs) with a transcriptional signature consistent with expression of immune checkpoints, or a low number of CTLs.

CONCLUSIONS: Combining nCRT with atezolizumab is feasible in patients with rEAC. Based on our exploratory biomarker study, future studies are necessary to elucidate the potential of neoadjuvant immunotherapy in patient subgroups.

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