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Incidence of immune checkpoint inhibitor-related colitis in solid tumor patients: A systematic review and meta-analysis.

ABSTRACT: Background: With the rising use of immune checkpoint inhibitors (ICI) across varying tumors types, immune-related colitis is an increasingly encountered, serious adverse event requiring appropriate management. The incidence across ICI treatment regimens and tumor types is unclear. Objective: To characterize the incidence of immune-related colitis among various ICI regimens and tumor types. Methods: Thirty-four original studies of prospective ICI trials were identified based on a PubMed search completed on November 1st, 2016. Seventeen studies compared incidences across tumor types. The incidences of all-grade, grade 3-4 (severe) colitis, and grade 3-4 (severe) diarrhea were collected. Results: Thirty-four studies containing 8863 patients were included in the meta-analysis. The overall incidence during ipilimumab monotherapy was 9.1% for all-grade colitis, 6.8% for severe colitis, and 7.9% for severe diarrhea. The incidence was lowest during PD-1/PD-L1 inhibitor monotherapy with 1.3% for all-grade colitis, 0.9% for severe colitis and 1.2% for severe diarrhea, while combination ipilimumab and nivolumab resulted in the highest incidences of all-grade colitis (13.6%), severe colitis (9.4%) and severe diarrhea (9.2%) among ICIs. Among melanoma, NSCLC, RCC patients, incidences of colitis and diarrhea with PD-1/PD-L1 inhibitor monotherapy did not significantly differ. Severe colitis incidence was similar with ipilimumab monotherapy at 3 mg/kg and 10 mg/kg (7.1% vs 5.1%, respectively), but significantly higher for severe diarrhea with 10mg/kg (11.5% vs 5.2%). Conclusions: The incidence of immune-related colitis and severe diarrhea was higher with ipilimumab-containing regimens compared with PD-1/PD-L1 inhibitors. There was no significant difference in immune-related colitis between different tumor types with PD-1/L1 inhibitors.

SUBMITTER: Wang DY

PROVIDER: S-EPMC5665065 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Incidence of immune checkpoint inhibitor-related colitis in solid tumor patients: A systematic review and meta-analysis.

Wang Daniel Y DY Ye Fei F Zhao Shilin S Johnson Douglas B DB

Oncoimmunology 20170705 10

Background: With the rising use of immune checkpoint inhibitors (ICI) across varying tumors types, immune-related colitis is an increasingly encountered, serious adverse event requiring appropriate management. The incidence across ICI treatment regimens and tumor types is unclear. Objective: To characterize the incidence of immune-related colitis among various ICI regimens and tumor types. Methods: Thirty-four original studies of prospective ICI trials were identified based ...[more]

PMID: 29123955

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Project description:BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used in cancer treatment, and a subset of patients undergo pseudoprogression. Recognizing the incidence of pseudoprogression is critical for clinical practice.PurposeTo evaluate by systematic review and meta-analysis the incidence of pseudoprogression in cancer treatment with ICIs, and compare the incidence according to response criteria, tumor types, and immunotherapeutic agents.Materials and MethodsMedline and Embase were searched to identify relevant studies published before December 31, 2018. Clinical trials, post hoc analysis of clinical trials, and prospective studies on ICI treatment in patients with malignant solid tumors were included. Pooled incidence of pseudoprogression for all included studies, per definition of pseudoprogression, cancer type, and drug type, was obtained by random-effects models with inverse variance weighting model.ResultsSeventeen studies with 3402 patients were analyzed. The pooled incidence of pseudoprogression was 6.0% (95% confidence interval: 5.0%, 7.0%). The definition of pseudoprogression were divided into four categories: progressive disease followed by partial response (PR) or complete response (CR) but not stable disease (SD) with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (six studies); progressive disease followed by SD or PR or CR with RECIST 1.1 (five studies); progressive disease followed by SD or PR or CR with RECIST 1.0 (three studies); and progressive disease followed by SD or PR or CR with immune-related response criteria (irRC) (three studies). Incidence of pseudoprogression varied from 4.5% to 8.0% per definition, ranged from 5.0% to 7.0% per cancer type, and was 5.6% with the monotherapy of programmed cell death-1 inhibitor.ConclusionThe overall incidence of pseudoprogression was 6.0% and was less than 10% in subgroup analyses according to the definitions of pseudoprogression, cancer type, and immune checkpoint inhibitor type. Varying definitions across trials and studies indicates the need for uniform criteria of pseudoprogression for solid tumors.© RSNA, 2020Online supplemental material is available for this article.See also the article by Dodd and MacDermott in this issue.

Project description:BackgroundWhile immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs, the prevalence of irAEs and potential risk factors have not been clarified. We identified irAE predictive factors and examined the relationship between the effect of ICIs and irAEs for patients with malignancies.MethodsA total of 533 cases treated with ICIs, including programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), for various malignancies were included retrospectively. We recorded irAEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 5. Prevalence and predictive factors associated with immune-related liver injury and the relationship between irAE and treatment response were analyzed.ResultsDuring a median of 10 (1-103) cycles with a median follow-up after several ICI initiations of 384 (21-1715) days, irAEs with all grades and with grade ≥ 3 developed in 144 (27.0%) and 57 (10.7%) cases. Cumulative irAE development rates were 21.9, 33.5, and 43.0% in all grades and 8.8, 14.9, and 20.7% in grade ≥ 3 at 5, 10, and 20 cycles, respectively. Patients who received anti-CTLA4 therapy were more likely to develop irAEs compared to those who received anti-PD-1 or anti-PD-L1 monotherapy. Liver injury was the most common irAE. Multivariate analysis identified the combination of PD-1 and anti-CTL-4 antibodies (hazard ratio [HR], 17.04; P < 0.0001) and baseline eosinophil count ≥130/μL (HR, 3.01 for < 130; P = 0.012) as independent risk factors for the incidence of immune-related liver injury with grade ≥ 2. Patients who developed irAEs had a higher disease control rate (P < 0.0001) and an increased overall survival rate compared to those without irAEs (P < 0.0001).ConclusionCombination therapy with anti-PD-1 and anti-CTL-4 antibodies resulted in higher a frequency of irAEs. Baseline absolute eosinophil count was found to be a predictive factor for immune-related liver injury. Occurrence of irAEs may be associated with higher efficacy of ICI treatment and longer survival among patients who receive ICI therapy.

Project description:ImportanceIf not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use of immune checkpoint inhibitor (ICI) regimens are unknown.ObjectiveTo compare the incidence and risk of endocrine AEs following treatment with US Food and Drug Administration-approved ICI regimens.Data sourcesA PubMed search through July 18, 2016, using the following keywords was performed: "ipilimumab," "MDX-010," "nivolumab," "BMS-963558," "pembrolizumab," "MK-3475," "atezolizumab," "MPDL3280A," and "phase."Study selectionThirty-eight randomized clinical trials evaluating the usage of these ICIs for treatment of advanced solid tumors were identified, resulting in a total of 7551 patients who were eligible for a meta-analysis. Regimens were categorized by class into monotherapy with a PD-1 (programmed cell death protein 1) inhibitor, a CTLA-4 (cytotoxic T-lymphocyte-associated protein-4) inhibitor, or a PD-L1 (programmed cell death 1 ligand 1) inhibitor, and combination therapy with PD-1 plus CTLA-4 inhibitors.Data extraction and synthesisThe data were extracted by 1 primary reviewer (R.B.-S.) and then independently reviewed by 2 secondary reviewers (W.T.B. and A.C.G.-C.) following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Inferences on the incidence of AEs were made using log-odds random effects models.Main outcomes and measuresIncidence of all-grade hypothyroidism, hyperthyroidism, hypophysitis, primary adrenal insufficiency, and insulin-deficient diabetes.ResultsOverall, 38 randomized clinical trials comprising 7551 patients were included in this systematic review and meta-analysis. The incidence of both hypothyroidism and hyperthyroidism was highest in patients receiving combination therapy. Patients on the combination regimen were significantly more likely to experience hypothyroidism (odds ratio [OR], 3.81; 95% CI, 2.10-6.91, P < .001) and hyperthyroidism (OR, 4.27; 95% CI, 2.05-8.90; P = .001) than patients on ipilimumab. Compared with patients on ipilimumab, those on PD-1 inhibitors had a higher risk of developing hypothyroidism (OR, 1.89; 95% CI, 1.17-3.05; P = .03). The risk of hyperthyroidism, but not hypothyroidism, was significantly greater with PD-1 than with PD-L1 inhibitors (OR, 5.36; 95% CI, 2.04-14.08; P = .002). While patients who received PD-1 inhibitors were significantly less likely to experience hypophysitis than those receiving ipilimumab (OR, 0.29; 95% CI, 0.18-0.49; P < .001), those who received combination therapy were significantly more likely to develop it (OR, 2.2; 95% CI, 1.39-3.60; P = .001). For primary adrenal insufficiency and insulin-deficient diabetes no statistical inferences were made due to the smaller number of events.Conclusions and relevanceOur study provides more precise data on the incidence of endocrine dysfunctions among patients receiving ICI regimens. Patients on combination therapy are at increased risk of thyroid dysfunction and hypophysitis.

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Incidence of immune checkpoint inhibitor-related colitis in solid tumor patients: A systematic review and meta-analysis.

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Incidence of immune checkpoint inhibitor-related colitis in solid tumor patients: A systematic review and meta-analysis.

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