Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma

J Immunother Cancer. 2022 Jan;10(1):e003497. doi: 10.1136/jitc-2021-003497.


Background: Programmed cell death 1 (PD-1) blockade induces tumor regression in patients with advanced esophageal squamous cell carcinoma (ESCC); however, little is known about the efficacy of PD-1 blockade as neoadjuvant therapy in resectable ESCC. We aim to assess the safety and feasibility of using the combination of neoadjuvant PD-1 blockade with chemotherapy in patients with ESCC.

Methods: Patients with previously untreated, resectable (stage II or III) ESCC were enrolled. Each patient received two 21-day cycles of neoadjuvant treatment with camrelizumab, nab-paclitaxel, and carboplatin before undergoing surgical resection approximately 6-9 weeks after the first cycle.

Results: Between January 2020 and September 2020, 37 patients were screened, of whom 23 were enrolled. The neoadjuvant therapeutic regimen had an acceptable side effect profile, and no delays in surgery were observed. Severe (grade 3-4) treatment-related adverse events included neutropenia (9 of 23, 39.1%) and leukopenia (2 of 23, 8.7%). The objective response and disease control rates were 90.5% and 100%, respectively. Twenty patients received surgery, and R0 resection was achieved in all cases. Five (25%) patients had a pathological complete response (PCR) and 10 (50%) patients had a major pathological response. The proportion of patients with a high tumor mutation burden and a high expression of programmed death-ligand 1 (PD-L1) in primary tumor was significantly higher in the PCR group than in the non-PCR group (p=0.044). The number of infiltrating PD-L1+ CD163+ cells was significantly lower in the PCR group than in the non-PCR group after treatment (p=0.017).

Conclusions: Neoadjuvant camrelizumab plus carboplatin and nab-paclitaxel had manageable treatment-related adverse effects and induced an objective response in 90.5% of patients, demonstrating its antitumor efficacy in resectable ESCC.

Trial registration number: ChiCTR2000028900.

Keywords: clinical trials as topic; combination; drug therapy; immunotherapy; investigational; therapies; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Esophageal Squamous Cell Carcinoma / drug therapy*
  • Esophageal Squamous Cell Carcinoma / surgery*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Tumor Microenvironment


  • Programmed Cell Death 1 Receptor

Associated data

  • ChiCTR/ChiCTR2000028900