Risk of cutaneous adverse events in cancer patients treated with phosphatidylinositol‐3‐kinase inhibitors: A systematic review and meta‐analysis of randomized controlled trials

BACKGROUND: Cutaneous adverse effects (AEs) are common following the phosphoinositide‐3‐kinase (PI3K) inhibitors treatment. We aim to estimate the incidence and risk of PI3K inhibitor‐related cutaneous AEs. METHODS: The protocol was submitted to the PROSPERO registry. We searched ClinicalTrials.gov and international databases up to July 29, 2022. Meta‐analysis was conducted by using risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Fourteen randomized controlled trials (RCTs) comprising 3877 patients were analyzed in this study. Compared with control arms, PI3K inhibitors showed a significant increase in the risk of all‐grade rash, high‐grade rash, and serious rash events (RR 2.29, 95% CI 1.58–3.31, p < 0.00001; RR 9.34, 95% CI 4.21–20.69, p < 0.00001; RR 5.11, 95% CI 2.11–12.36, p = 0.0003). The overall incidences of all‐grade rash and high‐grade rash were 26.2% (592/2257) and 4.4% (66/1487). Subgroup analyses of all‐grade rash according to cancer types and PI3K inhibitor assignations identified the significant associations. PI3K inhibitors also significantly increased the risk of pruritus and dry skin (RR 1.63, 95% CI 1.14–2.33, p = 0.007; RR 3.34, 95% CI 2.30–4.85, p < 0.00001), with incidences of 13.4% (284/2115) and 9.8% (141/1436) in the treatment group. CONCLUSION: There is a significantly increased risk of some cutaneous AEs in patients using PI3K inhibitors. Advance intervention is recommended in case of severe and life‐threatening events. Further research is required to investigate the risk factors and pathogenesis.