Risk of oral and gastrointestinal mucosal injury in patients with solid tumors treated with everolimus, temsirolimus or ridaforolimus: a comparative systematic review and meta-analysis

Abstract

Background: The authors performed a systematic review and meta-analysis of diarrhea and stomatitis associated with the use of everolimus, temsirolimus or ridaforolimus in patients with solid tumors. Patients and methods: Eligible studies included randomized trials of patients with solid tumors on everolimus, temsirolimus or ridaforolimus, describing the events of diarrhea and stomatitis. Results: After exclusion of ineligible studies, a total of 18 clinical trials including 8143 patients were considered eligible for the meta-analysis. The relative risk ratios of all-grade diarrhea and stomatitis were 1.94 (95% CI: 1.6–2.36; p < 0.00001) and 3.54 (95% CI: 2.59–4.84; p < 0.00001), respectively, while the relative risk ratios of high-grade diarrhea and stomatitis were 3.49 (95% CI: 2.39–5.09; p < 0.00001) and 6.98 (95% CI: 4.76–10.26; p < 0.00001), respectively. On subgroup analysis, there was no statistically significant difference between everolimus and temsirolimus in the risk of relevant adverse events. Conclusions: This meta-analysis demonstrated that regimens containing everolimus, temsirolimus or ridaforolimus for the treatment of solid tumors are associated with a significantly increased risk of all-grade and high-grade diarrhea and stomatitis. Close clinical monitoring is required when administering these drugs.

Keywords:

• diarrhea
• everolimus
• ridaforolimus
• stomatitis
• temsirolimus

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• We performed a systematic review and meta-analysis of diarrhea and stomatitis associated with the use of everolimus, temsirolimus or ridaforolimus in patients with solid tumors.

• Eligible studies included randomized trials of patients with solid tumors on everolimus, temsirolimus or ridaforolimus, describing the events of diarrhea and stomatitis.

• After exclusion of ineligible studies, a total of 18 clinical trials including 8143 patients were considered eligible for the meta-analysis.

• The relative risk ratios of all-grade diarrhea and stomatitis were 1.94 (95% CI: 1.6–2.36; p < 0.00001) and 3.54 (95% CI: 2.59–4.84; p < 0.00001), respectively.

• The relative risk ratios of high-grade diarrhea and stomatitis were 3.49 (95% CI: 2.39–5.09; p < 0.00001) and 6.98 (95% CI: 4.76–10.26; p < 0.00001), respectively.

• On subgroup analysis, we cannot spot a difference between everolimus and temsirolimus in the risk of relevant adverse events.

• Our meta-analysis has demonstrated that regimens containing everolimus, temsirolimus or ridaforolimus for the treatment of solid tumors are associated with a significantly increased risk of all-grade and high-grade diarrhea and stomatitis.