Social Science Research Network | 2021
Risks and Benefits of Anticancer Drugs in Advanced Cancer Patients: A Systematic Review and Meta-Analysis
Abstract
Background: Randomized clinical trials of anticancer drugs without active comparators are debated. The overall assessment of the trade-off between safety and efficacy would help to properly inform patients eligible for randomized clinical trials without active comparators. We aimed to quantify the safety and the efficacy of anticancer drugs in advanced cancer patients from randomized clinical trials without active comparators. \n \nMethods: This systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. A systematic literature search of English language publications from January 1, 2000, through January 7, 2021, was performed using MEDLINE (PubMed). Eligible trials included all randomized clinical trials evaluating anticancer drugs in adult patients with advanced cancers with a control arm without any anticancer drug consisting of BSC with or without a placebo. Clinical trials performed in the adjuvant, neoadjuvant or maintenance settings were excluded, as were clinical trials evaluating anticancer drugs in combination with radiotherapy. Two authors (C.M.B. and E.C.) independently reviewed the studies for inclusion. Data from published reports were extracted by investigators, and random-effects meta-analysis was performed to estimate the overall hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS). \n \nFindings: Of 3,551 studies screened, 128 eligible trials were found involving 47,432 patients. The HRs for PFS and OS were 0•58 [95%CI: 0•53–0•63] and 0•82 [95%CI: 0•78–0•85]. The absolute excesses in all grade, severe grade III-IV, and grade V (death) adverse events between the two arms were +13•9%, 10•2%, and +0•5%. A weak correlation was measured between the excess of severe toxicity and efficacy. \n \nInterpretation: Anticancer drugs evaluated in randomized clinical trials against no active treatment benefited trial participants. Severe toxicity did not significantly correlate with efficacy. \n \nFunding: None \n \nDeclaration of Interest: None