Neoadjuvant combination versus single-agent immune checkpoint inhibition in locally advanced MSI-H/dMMR colorectal cancer: A systematic review and meta-analysis
Abstract
e15595
Background:
Immune checkpoint inhibitors (ICIs) have transformed treatment for MSI-H/dMMR colorectal cancer (CRC). Neoadjuvant studies, including NICHE and NICHE-2, demonstrated high pathologic response rates with single-agent or combination ICI therapy. However, it is unknown whether combination ICI regimens improve pathologic complete response (pCR) rates compared to single-agent regimens or whether toxicity differs between combination and single-agent regimens.
Methods:
We systematically searched PubMed and the Cochrane Library for studies comparing neoadjuvant ICI combination therapy with single-agent therapy in MSI-H/dMMR locally advanced CRC. Pooled effect estimates were calculated using a random-effects model in R and reported as risk ratios (RR) with 95% confidence intervals (CI). Outcomes analyzed included pCR and treatment-related adverse events.
Results:
Three studies with 147 patients were included. Combination therapy significantly increased pCR compared with single-agent therapy (RR = 1.80; 95% CI, 1.32–3.46; p = 0.0002). Grade 3–4 immune-related adverse events were similar between groups (RR = 0.95; 95% CI, 0.17–5.33; p = 1.00); however, any-grade adverse events were higher with combination therapy (RR = 1.42; 95% CI, 1.05–1.93; p = 0.02). Conversely, bowel obstruction of any grade (RR = 1.54), bowel obstruction of grade 3 (RR = 1.52), enterocolitis (RR = 1.40), death (RR = 2.83), thyroid dysfunction of any grade (RR = 1.34), thyroid dysfunction of…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 147 participants or records.
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