Risk of selected gastrointestinal toxicities in cancer patients treated with MEK inhibitors; a comparative systematic review and Meta-analysis

Aim/Background

We performed a systematic review and meta-analysis of the risk of gastrointestinal (GI) toxicities associated with MEK inhibitors.

Methods

Eligible studies included randomized phase II and III trials of cancer patients on the three MEK inhibitors (trametinib, selumetinib and cobimetinib); describing events of stomatitis, diarrhea and vomiting.

Results

Our search strategy yielded 250 potentially relevant citations from Pubmed/Medline, Google scholar and CENTRAL Cochrane registry. After exclusion of ineligible studies, a total of 16 clinical trials were considered eligible for the meta-analysis. The relative risk (RR) of all-grade stomatitis, diarrhea and vomiting were 2.03 (95% CI 1.41-2.96; p = 0.002), 1.92(95% CI 1.48-2.50; p < 0.00001) and 1.35 (95% CI 1.06- 1.71; p = 0.01. Subgroup analyses according to agent used (trametinib vs. Selumetinib) and acccording to the cancer treated (melanoma vs. Non melanoma) did not reveal any significant difference between the subgroups.

Conclusions

Our meta-analysis has demonstrated that MEK inhibitor-based treatment is associated with an increased risk of stomatitis, diarrhea and vomiting compared to control. Clinicians should be aware of this risk and perform regular assessment.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.