Anticancer drugs versus supportive care for advanced esophageal cancer: a systematic review of randomized clinical trials and meta-analysis

Abstract Background Esophageal cancer (EC) is a global health concern and a leading cause of death. A large number of patients are diagnosed with advanced-stage EC, with very poor survival rates Anticancer drugs have limited effectiveness and severe side effects, but new therapies like immunotherapy show potential despite associated adverse events. This review aims to assess the efficacy and safety of anticancer drugs versus supportive care for advanced esophageal cancer (EC). Methods We searched (May 2022) MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Epistemonikos, and trial registries (ClinicalTrials.gov and PROSPERO) for randomised controlled trials (RCTs) comparing anticancer drugs (chemotherapy, immunotherapy, or biological/targeted therapy) with supportive care in advanced EC. The results were summarized using GRADE summary of finding tables. Results We included 15 RCTs. Most studies did not have a special focus on EC, did not detail the treatment lines in all patients, and did not evaluate all outcomes. Anticancer drugs may result in a slight increase in overall survival (OS) (HR 0.78; 95% CI 0.71, 0.86; MD 0.83 months) and better progression free survival (PFS) (HR 0.56 95% CI 0.49, 0.64, MD 0.68 months), but also may increase toxicity (RR 1.37; 95% CI 1.13, 1.65), without a significant improvement in quality of life. The certainty of evidence was low or very low due to indirectness of results and lack of specific focus on EC in some studies. Conclusion RCTs on advanced EC lack specificity, detailed treatment line information, and evaluation of all relevant outcomes. Moreover, when they find any benefit, this is negligible. Therefore, the certainty to justify anticancer drug treatments instead of BSC in advanced EC is low or very low and it is essential to weigh the potential benefits and risks carefully with active involvement of patients. Registration: The study protocol was registered in OSF (https://doi.org/10.17605/OSF.IO/7CHX6) on 2022-03-29.