Comparison of RECIST 1.1 and iRECIST in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: It is controversial whether iRECIST has a significant impact over RECIST 1.1 in evaluating the efficacy of immune checkpoint inhibitor treatment. We aimed to evaluate the impact of iRECIST on assessing treatment efficacy of immune checkpoint inhibitors over RECIST 1.1 through a systematic review and meta-analysis. Compared to RECIST 1.1, iRECIST had no impact on the overall response rate and disease control rate but detected 3.9% of patients with discordance in the date of progressive disease determination due to pseudoprogression and prolonged restricted mean progression-free survival time by 0.46 months. Therefore, the application of iRECIST had no impact on the response-related endpoints but had a minor impact on the survival endpoint, compared to RECIST 1.1. Such a modest benefit of iRECIST should be considered when we design a clinical trial for immune checkpoint inhibitors. ABSTRACT: Despite wide recognition of iRECIST, evidence regarding the impact of iRECIST over RECIST 1.1 is lacking. We aimed to evaluate the impact of iRECIST on assessing treatment efficacy of immune checkpoint inhibitors (ICIs) over RECIST 1.1. Articles that evaluated the treatment response and outcome based on both RECIST 1.1 and iRECIST were eligible. Data regarding overall response rates (ORR) and disease control rate (DCR) based on RECIST 1.1 and iRECIST, and data required to estimate individual patient data of progression-free survival (PFS) were extracted. Estimates were compared using meta-regression and pooled incidence rate ratios. The pooled difference of restricted mean survival time (RMST) of PFS between two criteria were calculated. Eleven studies with 6210 patients were analyzed. The application of iRECIST had no impact on the response-related endpoint by showing no significantly different ORR and DCR from RECIST 1.1 (pooled ORR, 23.6% and 24.7% [p = 0.72]; pooled DCR, 45.3% and 48.7% [p = 0.56] for iRECIST and RECIST 1.1, respectively) and had a minor impact on a survival endpoint by showing longer RMST of PFS than RECIST 1.1 (pooled difference, 0.46 months; 95% CI, 0.10–0.82 months; p = 0.01). Such a modest benefit of iRECIST should be considered when we design a clinical trial for immune checkpoint inhibitors.