PMID- 36593813 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231031 IS - 1108-7471 (Print) IS - 1792-7463 (Electronic) IS - 1108-7471 (Linking) VI - 36 IP - 1 DP - 2023 Jan-Feb TI - Diarrhea and colitis related to immune checkpoint inhibitor and BRAF/MEK inhibitor therapy. PG - 45-53 LID - 10.20524/aog.2023.0762 [doi] AB - BACKGROUND: Immune checkpoint inhibitor (ICI) therapy can be complicated by gastrointestinal adverse events (AEs). Similarly, gastrointestinal AEs have been reported with the use of serine/threonine-protein kinase B-Raf (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitor therapy. We investigated the characteristics and management of gastrointestinal AEs related to sequential ICI and BRAF/MEK inhibitor therapy. METHODS: We identified 255 adult cancer patients who received both BRAF/MEK inhibitor therapy and ICI therapy between 2014 and 2021. Thirty-two eligible patients had gastrointestinal AEs after receiving both therapies and were categorized based on the order of their administration. Their clinical characteristics, evaluation, treatment and outcomes were compared. RESULTS: Of the 32 eligible patients, 18 (56.3%) received ICI therapy followed by BRAF/MEK inhibitors (early ICI group), and 14 (44.8%) received BRAF/MEK inhibitor therapy followed by ICI (early BRAF/MEK inhibitor group). Compared with the early BRAF/MEK inhibitor group, the early ICI group had higher rates of grade 3-4 diarrhea (50.0% vs. 14.3%, P=0.047) and grade 3-4 colitis (38.9% vs. 0%, P=0.010). The early ICI group had a later onset of colitis (347.5 vs. 84.5 days, P=0.011) and a higher rate of hospitalization at initial colitis presentation (100% vs. 71.4%, P=0.028). Patients in the early ICI group were more likely to have diarrhea or colitis recurrence (69.2% vs. 9.1%, P=0.019) and re-hospitalization for colitis (38.9% vs. 0%, P=0.010). CONCLUSION: The sequential exposure of BRAF/MEK therapy after ICI may contribute to a more aggressive clinical profile of gastrointestinal toxicities that may warrant a more aggressive management strategy. CI - Copyright: (c) Hellenic Society of Gastroenterology. FAU - Kuang, Andrew G AU - Kuang AG AD - Department of Medicine, Baylor College of Medicine (Andrew G. Kuang, Kavea Panneerselvam). FAU - Mohajir, Wasay AU - Mohajir W AD - Department of Internal Medicine, The University of Texas Health Science Center at Houston (Wasay Mohajir). FAU - Panneerselvam, Kavea AU - Panneerselvam K AD - Department of Medicine, Baylor College of Medicine (Andrew G. Kuang, Kavea Panneerselvam). FAU - McQuade, Jennifer L AU - McQuade JL AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center (Jennifer L. McQuade, Isabella C. Glitz Oliva). FAU - Oliva, Isabella C Glitz AU - Oliva ICG AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center (Jennifer L. McQuade, Isabella C. Glitz Oliva). FAU - Khan, Muhammad Ali AU - Khan MA AD - Department of Gastroenterology, Hepatology, and Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center (Muhammad Ali Khan, Hao Chi Zhang, Anusha S. Thomas, Yinghong Wang), Houston, TX, USA. FAU - Zhang, Hao Chi AU - Zhang HC AD - Department of Gastroenterology, Hepatology, and Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center (Muhammad Ali Khan, Hao Chi Zhang, Anusha S. Thomas, Yinghong Wang), Houston, TX, USA. FAU - Thomas, Anusha S AU - Thomas AS AD - Department of Gastroenterology, Hepatology, and Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center (Muhammad Ali Khan, Hao Chi Zhang, Anusha S. Thomas, Yinghong Wang), Houston, TX, USA. FAU - Wang, Yinghong AU - Wang Y AD - Department of Gastroenterology, Hepatology, and Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center (Muhammad Ali Khan, Hao Chi Zhang, Anusha S. Thomas, Yinghong Wang), Houston, TX, USA. LA - eng PT - Journal Article DEP - 20221115 PL - Greece TA - Ann Gastroenterol JT - Annals of gastroenterology JID - 101121847 PMC - PMC9756030 OTO - NOTNLM OT - BRAF inhibitor OT - Immune checkpoint inhibitor OT - MEK inhibitor OT - colitis OT - immune-related adverse event COIS- Conflict of Interest: Y. Wang: consulting fee for Sorriso, MabQuest, Azur Rx EDAT- 2023/01/04 06:00 MHDA- 2023/01/04 06:01 PMCR- 2023/01/01 CRDT- 2023/01/03 01:54 PHST- 2022/05/30 00:00 [received] PHST- 2022/10/21 00:00 [accepted] PHST- 2023/01/03 01:54 [entrez] PHST- 2023/01/04 06:00 [pubmed] PHST- 2023/01/04 06:01 [medline] PHST- 2023/01/01 00:00 [pmc-release] AID - AnnGastroenterol-36-45 [pii] AID - 10.20524/aog.2023.0762 [doi] PST - ppublish SO - Ann Gastroenterol. 2023 Jan-Feb;36(1):45-53. doi: 10.20524/aog.2023.0762. Epub 2022 Nov 15.