Camrelizumab combined with apatinib for unresectable, metastatic esophageal squamous cell carcinoma: a single-center, single-arm, prospective study.

Background: The prognosis for esophageal cancer (EC), a common malignant tumor, is poor. The new oral small-molecule tyrosine kinase inhibitor apatinib has shown an excellent therapeutic effect on treating EC. Camrelizumab is a humanized programmed death 1 (PD-1) inhibitor with high affinity. Immune checkpoint inhibitors combined with chemotherapy have become the standard first-line treatment for advanced EC. The new combination strategy of anti-angiogenic therapy combined with immunotherapy has great application prospects in the treatment of tumors. We aimed to assess camrelizumab in combination with apatinib as a new combination regimen for advanced or metastatic esophageal squamous cell carcinoma (ESCC). Methods: In this study, we recruited patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, with pathologically confirmed unresectable, locally advanced, locally recurrent, or metastatic ESCC. Each patient received an intravenous infusion of camrelizumab 200 mg and oral administration of apatinib 250 mg once a day, every 21 days, as a cycle until disease progression, intolerance, or death. The primary endpoint was the objective response rate (ORR), while the Kaplan-Meier method and LIFETEST procedure were used to estimate survival functions for overall survival (OS) and progression-free survival (PFS). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used to evaluate adverse events. Results: Between December 1, 2019 and July 31, 2022, 35 patients were enrolled, with 29 patients in the efficacy and safety analysis. The ORR was 34.5%, and the disease control rate (DCR) reached 82.8%. Median OS was 13.8 months (95% CI: 11.2-16.2), and the estimated 6-, 9-, and 12-month OS rates were 85.5% (95% CI: 65.7-94.3%), 80.9% (95% CI: 60.3-91.5%), and 67.0% (95% CI: 43.8-82.4%), respectively. Median PFS was 9.5 months (95% CI: 7.0-13.6). The most prominent grade ≥3 adverse events associated with treatments were alanine aminotransferase (ALT) increase (10.3%), hypertension (10.3%), and reactive cutaneous capillary endothelial proliferation (CCEP) (6.9%), and no deaths occurred due to adverse events. Conclusions: Among patients with advanced or metastatic ESCC, camrelizumab combined with apatinib showed a reasonable remission rate and survival benefit with a manageable safety profile.

Association Between Polymorphisms in the Promoter Region of microRNA-34b/c and the Chemoradiotherapy Efficacy for Locally Advanced Esophageal Squamous Cell Carcinoma in Chinese Han Population.

The study aims to explore the association between polymorphisms in the promoter region of microRNA-34b/c (miR-34b/c) and the chemoradiotherapy efficacy for locally advanced esophageal squamous cell carcinoma (ESCC) in Chinese Han population. A total of 175 locally advanced ESCC cases and 186 healthy individuals were enrolled as the case and control groups. Denaturing high performance liquid chromatography (DHPLC) was applied to determine the genotypes of subjects. Subjects in the case group were classified into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). CR + PR were defined as the sensitive group, and SD + PD were defined as the resistance group. All patients were followed up for 3 ~ 36 months. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of rs4938723 in the promoter region of miR-34b/c in the chemoradiotherapy efficacy for patients with locally advanced ESCC. The distribution of genotype and allele of rs4938723 in the promoter region of miR-34b/c was significantly different between the case and control group (both P < 0.05), and CC genotype and C allele could decrease the risk of ESCC (CC genotype: OR = 0.57, 95%CI = 0.32 ~ 0.99, P = 0.045; C allele: OR = 0.72, 95%CI = 0.54 ~ 0.97, P = 0.032). MiR-34b/c rs4938723 was associated with ESCC TNM staging, differentiation degree, and lymph node metastasis (LNM) for ES CC patients (all P < 0.05). The chemoradiotherapy efficacy of patients with CC genotype was better than that of patients with (TT + TC) genotypes (P < 0.05). ROC curve results showed that the area under curve (AUC), sensitivity and specificity were 0.777, 85.1% and 71.3%, respectively. The average median progression free survival (PFS) of patients with (TT + TC) genotypes was significantly shorter than those patients with CC genotype (P < 0.05). Our study provides evidence that miR-34b/c rs4938723 is closely related with the chemoradiotherapy efficacy for locally advanced ESCC.