TY - JOUR
T1 - Diarrhea and colitis related to immune checkpoint inhibitor and BRAF/MEK inhibitor therapy
AU - Kuang, Andrew G.
AU - Mohajir, Wasay
AU - Panneerselvam, Kavea
AU - McQuade, Jennifer L.
AU - Oliva, Isabella C.Glitz
AU - Khan, Muhammad Ali
AU - Zhang, Hao Chi
AU - Thomas, Anusha S.
AU - Wang, Yinghong
N1 - Funding Information:
Medical editing of this paper was provided by Editing Services, Research Medical Library, at The University of Texas MD Anderson Cancer Center.
Publisher Copyright:
© 2023 Hellenic Society of Gastroenterology.
PY - 2023/12/25
Y1 - 2023/12/25
N2 - 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 therapand ICI therapy between 2014 and 2021. Thirty-two eligible patients had gastrointestinal AEs aftereceiving both therapies and were categorized based on the order of their administration. Theiclinical 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 aggreclinical profile of gastrointestinal toxicities that may warrant a more aggressive management strategy.
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 therapand ICI therapy between 2014 and 2021. Thirty-two eligible patients had gastrointestinal AEs aftereceiving both therapies and were categorized based on the order of their administration. Theiclinical 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 aggreclinical profile of gastrointestinal toxicities that may warrant a more aggressive management strategy.
KW - BRAF inhibitor
KW - colitis
KW - Immune checkpoint inhibitor
KW - immune-related adverse event
KW - MEK inhibitor
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U2 - 10.20524/aog.2023.0762
DO - 10.20524/aog.2023.0762
M3 - Article
C2 - 36593813
AN - SCOPUS:85144693616
SN - 1108-7471
VL - 36
SP - 45
EP - 53
JO - Annals of Gastroenterology
JF - Annals of Gastroenterology
IS - 1
ER -