Risk of mucocutaneous toxicities in patients with solid tumors treated with everolimus; a systematic review and meta-analysis

Background: We performed a systematic review and meta-analysis of mucocutaneous toxicities associated with the use of everolimus in solid tumors. Patients and methods: Eligible studies included randomized Phase II and III trials of patients with solid tumors on everolimus; describing events of stomatitis, skin rash, pruritus and mouth ulceration. Results: Our search strategy yielded 380 potentially relevant citations on everolimus from Pubmed/Medline, CENTRAL Cochrane registry and American Society of Clinical Oncology meeting library. After exclusion of ineligible studies, a total of 10 clinical trials were considered eligible for the meta-analysis, including eight Phase III trials and two Phase II trials. The relative risk of all-grade stomatitis, skin rash, pruritus and mouth ulceration were 3.86(95% CI: 2.23-6.68; p < 0.001); 3.49(95% CI: 2.39-5.08; p < 0.0001); 2.85(95% CI: 2.04-3.97; p = 0.0001); 3.31 (95% CI: 1.46-7.50; p = 0.004); respectively. Exploratory subgroup analysis showed no effect of tumor types or treatment regimen on the relative risk of the relevant adverse events. Conclusion: Our meta-analysis has demonstrated that everolimus is associated with a significantly increased risk of all-grade stomatitis, skin rash, and pruritus and mouth ulceration. Clinicians should be aware of these risks and perform early clinical assessment and intervene accordingly.