Adjuvant chemoradiotherapy plus pembrolizumab for locally advanced esophageal squamous cell carcinoma with high risk of recurrence following neoadjuvant chemoradiotherapy: a single-arm phase II study.

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  • Additional Information
    • Source:
      Publisher: Springer Verlag Country of Publication: Germany NLM ID: 8605732 Publication Model: Electronic Cited Medium: Internet ISSN: 1432-0851 (Electronic) Linking ISSN: 03407004 NLM ISO Abbreviation: Cancer Immunol Immunother Subsets: MEDLINE
    • Publication Information:
      Publication: Berlin : Springer Verlag
      Original Publication: Berlin ; New York, NY : Springer International, c1982-
    • Subject Terms:
      Antibodies, Monoclonal, Humanized*/therapeutic use ; Antibodies, Monoclonal, Humanized*/administration & dosage ; Antibodies, Monoclonal, Humanized*/adverse effects ; Esophageal Squamous Cell Carcinoma*/therapy ; Esophageal Squamous Cell Carcinoma*/mortality ; Esophageal Squamous Cell Carcinoma*/pathology ; Esophageal Neoplasms*/therapy ; Esophageal Neoplasms*/mortality ; Esophageal Neoplasms*/pathology ; Neoplasm Recurrence, Local*/therapy ; Neoadjuvant Therapy*/methods ; Chemoradiotherapy, Adjuvant*/methods; Humans ; Male ; Middle Aged ; Female ; Aged ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Esophagectomy
    • Abstract:
      Background: Adjuvant nivolumab reduces recurrence in patients with locoregional esophageal cancer who had pathological residual disease after neoadjuvant chemoradiotherapy and R0 resection. However, the efficacy of adjuvant anti-PD-1 therapy in patients at higher risk of recurrence remains unclear.
      Methods: This phase II trial (ClinicalTrials.gov identifier: NCT03322267) enrolled patients with locally advanced esophageal squamous cell carcinoma (ESCC) received neoadjuvant chemoradiotherapy plus esophagectomy but still had various risk factors for recurrence, such as involved or close margins (≤ 1 mm), extranodal extension of the involved lymph nodes, and the ypN2-3 stage. Patients received adjuvant therapy composed of a course of cisplatin-based chemoradiotherapy and pembrolizumab (200 mg, IV every 3 weeks) for 18 cycles. The primary endpoint was 1-year relapse-free survival (RFS) rate.
      Results: Twenty-five patients were enrolled. The risk factors were tumor margins of ≤ 1 mm (18 patients), extranodal extension of the involved lymph nodes (9 patients), and the ypN2-3 stage (9 patients). The median follow-up duration was 21.6 months (95% CI: 18.7-33.2). The rate of 1-year RFS was 60.0%. The median duration of RFS and overall survival was 14.3 (95% CI: 9.0-19.5) and 21.6 (95% CI: 0.0-45.5) months, respectively. Treatment-emergent adverse events of any grade and those of ≥ 3 grade occurred in 56% and 8% of all patients receiving cisplatin-based chemoradiotherapy and in 79.2% and 12.5% of those receiving pembrolizumab.
      Conclusions: Adjuvant chemoradiotherapy followed by pembrolizumab is feasible and may be associated with improved 1-year RFS rate in patients at high risk of recurrence after trimodality therapy for locally advanced ESCC. Trial registration number ClinicalTrials.gov (No. NCT03322267).
      (© 2024. The Author(s).)
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    • Grant Information:
      MISP# 55717 Merck Sharp & Dohme
    • Contributed Indexing:
      Keywords: Adjuvant therapy; Esophageal squamous cell carcinoma; High risk; Immune checkpoint inhibitor; Pembrolizumab
    • Molecular Sequence:
      ClinicalTrials.gov NCT03322267
    • Accession Number:
      DPT0O3T46P (pembrolizumab)
      0 (Antibodies, Monoclonal, Humanized)
    • Publication Date:
      Date Created: 20240909 Date Completed: 20240909 Latest Revision: 20241026
    • Publication Date:
      20241026
    • Accession Number:
      PMC11383884
    • Accession Number:
      10.1007/s00262-024-03826-y
    • Accession Number:
      39249605