PD‐1/PD‐L1 based immunochemotherapy versus chemotherapy alone for advanced esophageal squamous cell carcinoma: A meta‐analysis focus on PD‐L1 expression level

Abstract Background Immunochemotherapy has become a new treatment for advanced esophageal squamous cell carcinoma (ESCC). Aims We aimed to study the clinical efficacy and toxicity of immunochemotherapy based on PD‐1/PD‐L1 compared with chemotherapy alone in the treatment of advanced ESCC, focusing on analyzing the influence of PD‐L1 expression level. Methods and Results Five randomized controlled trials comparing PD‐1/PD‐L1 based immunochemotherapy with chemotherapy alone for advanced ESCC were included. We extracted efficacy data (objective response rate [ORR], disease control rate [DCR], overall survival [OS] rate, progression‐free survival [PFS] rate) and safety data (treatment‐related adverse events, treatment‐related mortality) and performed meta‐analyses. Compared with chemotherapy alone, the ORR and DCR of immunochemotherapy increased by 2.05 times and 1.54 times, respectively. Overall, patients receiving immunochemotherapy had a significant long‐term survival advantage (OS: hazard ratio [HR] = 0.68, 95% confidence intervals [CI] 0.61–0.75; PFS: HR = 0.62, 95% CI 0.55, 0.70, respectively). Even with PD‐L1 tumor proportion score <1%, immunochemotherapy also showed a significant survival advantage (OS: HR = 0.65, 95% CI 0.46–0.93; PFS: HR = 0.56, 95% CI 0.46–0.69, respectively). However, for PD‐L1 combined positive score (CPS) < 1, the survival advantage of immunochemotherapy was not significant (OS: HR = 0.89, 95% CI 0.42–1.90; PFS: HR = 0.71, 95% CI 0.47–1.08, respectively). The toxicity of immunochemotherapy was higher than that of chemotherapy alone, but there was no statistical difference in treatment‐related mortality (odds ratio = 1.11, 95% CI 0.67–1.83). Conclusion In this study, treatment‐related mortality was similar between immunochemotherapy and chemotherapy. PD‐1/PD‐L1 based immunochemotherapy significantly could improve survival outcomes in patients with advanced ESCC. For patients with CPS <1, the survival advantage of immunochemotherapy was not significant compared with chemotherapy

Narrative review of pembrolizumab for the treatment of esophageal cancer: evidence and outlook

International audienceObjective: Based on the current evidence, review the efficacy and safety profile of pembrolizumab, along with its shortcomings, in an effort to define future research directions. Background: The survival outcome of esophageal cancer (EC) is poor, especially in patients with advanced stage. Palliative surgery, chemotherapy, radiotherapy and chemoradiotherapy have limited efficacy in prolonging the survival time. Currently, immunotherapies, including adoptive cell therapy-based, antibodybased, and vaccine-based therapies, are attracting considerable attention. The mechanism of immunotherapy lies in the modification of immune response and prevention of immune escape. Immunomodulatory agents can block the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway, thereby allowing lymphocytes to attack tumor cells. This class of drugs has the potential to treat a variety of tumors and may substantially improve overall survival (OS) in some patients. Multiple clinical trials have shown that pembrolizumab has good efficacy and safety, enhances the EC treatment paradigm, and has even become the first-line treatment of choice for patients with PD-L1-positive recurrent or metastatic EC. Methods: We reviewed the results of clinical trials of pembrolizumab for EC and gastroesophageal cancer presented at Embase, PubMed, the American Society of Clinical Oncology (ASCO) annual meetings, and the Cochrane Central Register of Controlled Trials. Conclusions: Pembrolizumab has good efficacy and tolerability profiles, and has emerged as a second-line option for the treatment of PD-L1-positive locally advanced or metastatic ESCC. Pembrolizumab has many promising applications, and further investigations into its mechanisms should be conducted

Left atrial concomitant surgical ablation for treatment of atrial fibrillation in cardiac surgery: A meta-analysis of randomized controlled trials

<div><p>Introduction</p><p>Surgical ablation is a generally established treatment for patients with atrial fibrillation undergoing concomitant cardiac surgery. Left atrial (LA) lesion set for ablation is a simplified procedure suggested to reduce the surgery time and morbidity after procedure. The present meta-analysis aims to explore the outcomes of left atrial lesion set versus no ablative treatment in patients with AF undergoing cardiac surgery.</p><p>Methods</p><p>A literature research was performed in six database from their inception to July 2017, identifying all relevant randomized controlled trials (RCTs) comparing left atrial lesion set versus no ablative treatment in AF patient undergoing cardiac surgery. Data were extracted and analyzed according to predefined clinical endpoints.</p><p>Results</p><p>Eleven relevant RCTs were included for analysis in the present study. The prevalence of sinus rhythm in ablation group was significantly higher at discharge, 6-month and 1-year follow-up period. The morbidity including 30 day mortality, late all-cause mortality, reoperation for bleeding, permanent pacemaker implantation and neurological events were of no significant difference between two groups.</p><p>Conclusions</p><p>The result of our meta-analysis demonstrates that left atrial lesion set is an effective and safe surgical ablation strategy for AF patients undergoing concomitant cardiac surgery.</p></div

Forest plot of neurological events, showing summary ORs with 95% confidence intervals for included studies.

<p>Forest plot of neurological events, showing summary ORs with 95% confidence intervals for included studies.</p

Forest plot of sinus rhythm prevalence at discharge, 6-month, and 1 year follow-up, showing summary of ORs with 95% confidence intervals for included studies.

<p>Forest plot of sinus rhythm prevalence at discharge, 6-month, and 1 year follow-up, showing summary of ORs with 95% confidence intervals for included studies.</p