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Gastrointestinal, pancreatic, and hepatic toxicity profile of CTLA-4 immune checkpoint inhibitors alone and in combination with PD-1/PD-L1 inhibitors: A meta-analysis of clinical trials
- Source :
- Journal of Clinical Oncology. 37:e14117-e14117
- Publication Year :
- 2019
- Publisher :
- American Society of Clinical Oncology (ASCO), 2019.
-
Abstract
- e14117 Background: Cytotoxic T-lymphocyte activator-4 immune checkpoint inhibitors (CTLA-4-ICPI) is believed to cause more toxicity than programmed cell death/Ligand-1 (PD-1/PD-L1) ICPIs. We conducted a meta-analysis to outline the gastrointestinal (GI), pancreatic, and hepatic toxicity of CTLA-4 ICPIs when used alone and in combination with PD-1/PD-L1 ICPIs (C-ICPI). Methods: Ovid MEDLINE, EMBASE, Cochrane Library, SCOPUS, Web of Science, ClinicalTrials.gov, and WHO ICTRP were queried from January 2007-October 2018. Clinical trials reporting ICPI associated adverse events (AEs) were included. Colitis was defined as the development of diarrhea or documented colitis of any grade. Pancreatitis was defined as an elevation of amylase or lipase. Hepatitis was defined as elevation of ALT, AST, or transaminitis of any grade. A meta-analysis of proportions was conducted to report pooled AEs rate with 95% confidence intervals (CI) using a random effects model. Results: Overall, 30 study arms (20 CTLA-4, 10 C-ICPI) enrolling 3721 patients were included. There were a total of 3944 and 3317 AEs with CTLA-4 and C-ICPI use, respectively, with a pooled incidence of high grade AEs (grade 3-5; HAEs) of 23% (95% CI 16-33%) with CTLA-4 use and 52% (95% CI 37-67%) with C-ICPI use ( Table). The incidence of high-grade colitis was higher among patients treated with CTLA-4 ICPI. The proportion of high-grade pancreatitis was higher among patient who received C-ICPI. Two GI perforations were reported with CTLA-4 use. Pooled incidence of treatment related mortality was 1% in both groups. Conclusions: Though the overall GI, hepatic and pancreatic safety profile of CTLA-4 is comparable to C-ICPI, a higher incidence of high-grade colitis was found with CTLA-4. Two GI perforations were reported with CTLA-4 and warrant further investigation. No difference in treatment related mortality was found among the two groups. [Table: see text]
- Subjects :
- Cancer Research
Programmed cell death
biology
business.industry
Immune checkpoint inhibitors
Clinical trial
03 medical and health sciences
0302 clinical medicine
Oncology
CTLA-4
030220 oncology & carcinogenesis
PD-L1
Meta-analysis
Toxicity
Cancer research
biology.protein
Medicine
Cytotoxic T cell
business
030215 immunology
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi...........a332e83f9743b4a2e94b6e69a6328f38