Abstract
Background: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy can improve clinical outcomes in the treatment of various tumors, but may also be associated with more adverse events (AEs). We performed a systematic review and meta-analysis to characterize the risk of gastrointestinal AEs in cancer patients treated with ICI plus chemotherapy.Methods: This review was based on comprehensive search through PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) that reported gastrointestinal AEs following the use of ICI plus chemotherapy. Literature screening, data extraction, and quality evaluation were performed by two individual reviewers. Revman (version 5.3) was used for meta-analysis. Risk ratios (RR) with 95% confidence interval (CI) were calculated. Meta-analysis was conducted according to different types of ICIs [programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors].Results: After a full-text review, 10 trials involving 5,142 patients were included in the study. Compared with chemotherapy alone, PD-1 inhibitor plus chemotherapy significantly increased the risk of diarrhea (RR = 1.38, 95% CI, 1.13–1.68, P = 0.001; I2 = 0%) and colitis (RR = 2.90, 95% CI, 1.02–8.21, P = 0.050; I2 = 0%), PD-L1 inhibitor plus chemotherapy significantly increased the risk of nausea (RR = 1.17, 95% CI, 1.02-1.35, P = 0.020; I2 = 0%), while CTLA-4 inhibitor plus chemotherapy significantly increased the risk of decreased appetite (RR = 1.49, 95% CI, 1.17–1.90, P = 0.001; I2 = 0%), diarrhea (RR = 2.23, 95% CI, 1.90–2.63, P < 0.00001; I2 = 0%), and colitis (RR = 28.39, 95% CI, 5.59–144.24, P < 0.001; I2 = 0%).Conclusions: This meta-analysis demonstrated that ICI plus chemotherapy is associated with a higher risk of gastrointestinal AEs. However, combining different ICIs may lead to diverse gastrointestinal toxicities. Clinicians should be aware of these AEs in the application of ICI plus chemotherapy.
Highlights
Cancer therapy has made great progress with the advance of immune checkpoint inhibitors (ICIs) including cytotoxic Tlymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1), and programmed death ligand 1 (PD-L1) inhibitors
We found that patients treated with PD-L1 inhibitor plus chemotherapy experienced no significantly more decreased appetite events compared with those with chemotherapy monotherapy (RR = 1.48, 95% confidence intervals (CIs), 0.94–2.34, P = 0.090; I2 = 0%) (Figure 6A)
Our study demonstrated that the gastrointestinal adverse events (AEs) profile observed was as expected on the basis of the known events, such as nausea, vomiting, diarrhea, constipation, decreased appetite, and colitis
Summary
Cancer therapy has made great progress with the advance of immune checkpoint inhibitors (ICIs) including cytotoxic Tlymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1), and programmed death ligand 1 (PD-L1) inhibitors. They have been approved for the treatment of melanoma, metastatic renal cell carcinoma (RCC), non–small-cell lung cancer (NSCLC), head and neck cancer, and hematological system diseases [1,2,3,4,5,6,7]. The combination of immune checkpoint inhibitors (ICIs) and chemotherapy can improve clinical outcomes in the treatment of various tumors, but may be associated with more adverse events (AEs). We performed a systematic review and meta-analysis to characterize the risk of gastrointestinal AEs in cancer patients treated with ICI plus chemotherapy
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