Cutaneous Toxic Effects in tumor patients treated with Programmed Cell Death Protein-1 checkpoint inhibitors and/or Programmed Death-Ligand 1 checkpoint inhibitors and its association with survival: a systematic review and meta-analysis

Abstract Objective To systematically review the cohort studies about the relation between immune-related Cutaneous Adverse Events(irCAEs) and clinical benefit in patients treated with Programmed Cell Death Protein-1(PD-1)/Programmed Death-Ligand 1(PD-L1) inhibitors through meta-analysis. Methods PubMed, Embase, Cochrane database, China National Knowledge Infrastructure, Wanfang Database of China Science Periodical Database and Chongqing VIP were searched for cohort studies from inception to 1 November 2020. The primary outcomes were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were examined as secondary outcomes. A pooled relative risk (RR) and hazard ratio (HR) with 95% confidence intervals (CI) were calculated. Results Nine studies (2105 participants) were included. Compared with non-irCAEs patients treated with PD-1/PD-L1 inhibitors, the ORR of patients with irCAEs was higher (RR 2.38, 95% CI 1.91 to 2.98). Patients occurred irCAEs were more likely to report CR (RR 3.68, 95% CI 0.67 to 20.14), PR (RR 3.11, 95% CI 1.95 to 4.96), and SD (RR 1.11, 95% CI 0.79 to 1.55), and less likely to get PD (RR 0.39, 95% CI 0.19 to 0.80). For survival data, irCAEs development was significantly associated with both PFS (HR 0.37, 95% CI 0.29 to 0.48) and OS (HR 0.50, 95% CI 0.42 to 0.60). Conclusions The occurrence of irCAEs was associated with a lower risk of tumor progression or death. Awareness of irCAEs is important as an indicator of robust antitumor immunity and associated improved survival. Systematic review registration: PROSPERO CRD42021250251.