title: Risk of selected gastrointestinal toxicities in cancer patients treated with MEK inhibitors: a comparative systematic review and meta-analysis.
abstract: We performed a systematic review and meta-analysis of the risk of gastrointestinal (GI) toxicities associated with MEK inhibitors. 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. 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 risks 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), the regimen used (monotherapy vs combination) and the cancer treated (melanoma vs nonmelanoma) did not reveal any significant difference between the subgroups. 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.
authors.affiliation: a 1 Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Rahman
authors.affiliation: a 1 Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Hesham
authors.initials: H
authors.lastname: ElHalawani
authors.affiliation: b 2 Clinical Oncology Department, Nasser Institute, Cairo, Egypt.
authors.forename: Hoda
authors.initials: H
authors.lastname: Ahmed
authors.affiliation: a 1 Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ellithy
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D016009:Chi-Square Distribution; D003967:Diarrhea / Q000139:chemically induced / Q000201:enzymology; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000201:enzymology; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D016017:Odds Ratio; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D013280:Stomatitis / Q000139:chemically induced / Q000201:enzymology; D014839:Vomiting / Q000139:chemically induced / Q000201:enzymology
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: cobimetinib; diarrhea; selumetinib; stomatitis; trametinib