Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial.
Nat Med, 2023/08;29(8):2068-2078.
Yin J[1], Yuan J[2, 3, 4], Li Y[2, 4], Fang Y[1], Wang R[2], Jiao H[1], Tang H[1], Zhang S[1], Lin S[1], Su F[1], Gu J[1], Jiang T[1], Lin D[1], Huang Z[1, 5], Du C[1, 5], Wu K[6, 7, 8], Tan L[9, 10], Zhou Q[11, 12, 13]
Affiliations
PMID: 37488287DOI: 10.1038/s41591-023-02469-3
Impact factor: 87.241
Abstract
Overall survival (OS) benefits of neoadjuvant immunotherapy remain elusive in locally advanced esophageal squamous cell carcinomas (ESCC). Here, we reported the results of a phase 1b trial of neoadjuvant PD-L1 blockade with adebrelimab in resectable ESCC. Patients received two neoadjuvant doses of adebrelimab followed by surgery. The primary endpoints were safety and feasibility; secondary endpoints included pathologic complete response (pCR) and OS. Our data showed the primary endpoints of safety and feasibility had been met. Common treatment-related adverse events were anorexia (32%) and fatigue (16%), without grade 3 or more adverse events. Of the 30 patients enrolled in the trial, 25 underwent successful resection without surgery delay and 24% had major pathologic responses including a pCR rate of 8%. The 2-year OS was 92%. Responsive patients had an immune-enriched tumor microenvironment phenotype, whereas nonresponsive patients had greater infiltration of cancer-associated fibroblasts at baseline. Clonotypic dynamics of pre-existing intratumoral T cells was a hallmark of responsive patients. These findings provide a rational for neoadjuvant anti-PD-L1 monotherapy as a therapeutic strategy for patients with resectable ESCC. ClinicalTrials.gov identifier: NCT04215471 .
MeSH terms
Humans; Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; Cisplatin; Neoadjuvant Therapy; Treatment Outcome; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Tumor Microenvironment
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