Chemoradiotherapy and Subsequent Immunochemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II NEXUS-1 Trial

Clin Cancer Res. 2024 Nov 15;30(22):5061-5072. doi: 10.1158/1078-0432.CCR-24-1236.

Abstract

Purpose: This phase II trial investigated the safety and efficacy of chemoradiotherapy (CRT) followed by immunochemotherapy (iCT) and surgery in unresectable locally advanced esophageal squamous cell carcinoma (ESCC).

Patients and methods: Patients with unresectable locally advanced ESCC received radiotherapy (50 Gy/25f, 5 days/week) and nab-paclitaxel (100 mg on day 1/week) plus cisplatin (25 mg/m2 on day 1/week) for 5 weeks, followed by tislelizumab (200 mg on day 1/cycle) plus chemotherapy (nab-paclitaxel 150 mg/m2 and cisplatin 75 mg/m2 on day 2/cycle) for two 21-day cycles. Patients who converted to resectable underwent surgery 2 to 4 weeks afterward. The primary endpoint was a 1-year progression-free survival (PFS) rate.

Results: Thirty patients were enrolled and underwent CRT (median follow-up: 21 months), of whom 24 received iCT. Twenty (66.7%) patients achieved resectability (R0: 95.2%; pathologic complete response: 65.0%; major pathologic response: 90.0%). One-year PFS and overall survival (OS) rates were 79.4% and 89.6%, respectively. The R0 resection group exhibited longer PFS (median, not reached vs. 8.4 months; HR = 0.28; 95% confidence interval, 0.08-0.84; P = 0.02) and OS (median, not reached vs. 19.2 months; HR = 0.18; 95% confidence interval, 0.04-0.73; P < 0.01) than the nonsurgery group. Grade 3 to 4 adverse events were observed in 11 (11/30, 36.7%) patients, and immune-related pneumonitis was observed in 5 (5/24, 20.8%) patients. Post-CRT minimal residual disease before surgery was associated with unfavorable PFS and OS.

Conclusions: Our study met the primary endpoint. Conversion CRT and subsequent iCT followed by surgery was a promising treatment strategy for unresectable locally advanced ESCC.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Albumins / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Chemoradiotherapy* / methods
  • Cisplatin / administration & dosage
  • Esophageal Neoplasms* / mortality
  • Esophageal Neoplasms* / pathology
  • Esophageal Neoplasms* / therapy
  • Esophageal Squamous Cell Carcinoma* / mortality
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Esophageal Squamous Cell Carcinoma* / therapy
  • Female
  • Humans
  • Immunotherapy / methods
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Paclitaxel / administration & dosage
  • Progression-Free Survival

Substances

  • Cisplatin
  • Paclitaxel
  • Albumins
  • 130-nm albumin-bound paclitaxel