Consolidative camrelizumab following definitive concurrent chemoradiotherapy with involved-field irradiation in locally advanced esophageal squamous cell carcinoma: a single-arm phase 2 trial.

Abstract

Definitive concurrent chemoradiotherapy (dCCRT) is considered the standard treatment for locally advanced unresectable esophageal squamous cell carcinoma (ESCC). However, approximately half of patients still experience local recurrence or distant metastasis. The CheckMate 577 trial demonstrated that adjuvant nivolumab significantly improves disease-free survival in patients with resected esophageal or gastroesophageal junction cancer after neoadjuvant chemoradiotherapy. However, the role of consolidation immunotherapy in locally advanced unresectable esophageal cancer remains unclear. Camrelizumab, an anti-programmed death receptor 1 (PD-1) antibody, has shown antitumor activity in advanced or metastatic esophageal squamous cell carcinoma. We conducted a clinical trial to evaluate the efficacy of camrelizumab consolidation therapy in patients with unresectable, locally advanced ESCC following dCCRT. This single-arm, phase II trial was conducted at the Fourth Hospital of Hebei Medical University (Shijiazhuang, China). Eligible patients were aged 18-75 years with histopathologically confirmed, locally advanced (T1bN+M0, T2-4N0-2M0, or supraclavicular lymph node metastasis) unresectable or medically inoperable ESCC, who had not experienced disease progression after completing dCCRT. Patients received camrelizumab consolidation therapy (200 mg intravenously [iv], day 1, every 2 weeks [q2w]) for 12 months. After 12 months, patients could independently choose to continue immunotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included disease control rate (DCR), objective response rate (ORR), duration of response (DoR), overall survival (OS) and safety. Between April 2020 and November 2023, 43 patients were screened, 35 were enrolled, and 32 were included in the analysis. As of the data cut-off date (July 25, 2025), 12 patients had experienced disease progression, and 10 patients had died. The DCR was 59.4% (19/32). Neither the median PFS nor the median OS was reached. The 1-year, 2-year, and 3-year PFS rates were 81.3%, 62.5%, and 62.5%, respectively. The 1-year, 2-year, and 3-year OS rates were 96.9%, 77.7%, and 63.0%, respectively. Regarding safety, most adverse events (AEs) were grade 1-2. The most common AEs were anemia (68.8%), leukopenia (50.0%), and reactive cutaneous capillary endothelial proliferation (43.8%). Grade 3 AEs included leukopenia (12.5%) and thrombocytopenia (3.1%). No treatment-related deaths occurred. The incidence of pneumonitis in the cohort was 31.3%; all cases were grade 1-2, with no grade ≥3 pneumonitis observed. Consolidation camrelizumab following definitive concurrent chemoradiotherapy with involved-field irradiation demonstrates promising efficacy and manageable toxicity in patients with unresectable locally advanced ESCC. The trial is registered on ClinicalTrials.gov (NCT04286958).