Pretreatment body mass index and clinical outcomes in cancer patients following immune checkpoint inhibitors: a systematic review and meta-analysis

BackgroundIncreased body mass index (BMI) has been associated with improved response to immune checkpoint inhibitors (ICIs) in multiple cancer types. We evaluated associations between BMI, ICI dosing strategy, and clinical outcomes.MethodsWe abstracted clinical data on patients with cancer treated with ICI, including age, sex, cancer type, BMI, ICI type, dosing strategy (weight-based or fixed), radiographic response, overall survival (OS), and progression-free survival (PFS). We compared clinical outcomes between low-BMI and high-BMI populations using Kaplan-Meier curves, Cox regressions, and Pearson product-moment correlation coefficients.ResultsA total of 297 patients were enrolled, of whom 40% were women and 59% were overweight (BMI≥25). Of these, 204 (69%) received fixed and 93 (31%) received weight-based ICI dosing. In the overall cohort, overweight BMI was associated with improved PFS (HR 0.69; 95% CI 0.51 to 0.94; p=0.02) and had a trend toward improved OS (HR 0.77; 95% CI 0.57 to 1.04; p=0.08). For both endpoints, improved outcomes in the overweight population were limited to patients who received weight-based ICI dosing (PFS HR 0.53; p=0.04 for weight-based; vs HR 0.79; p=0.2 for fixed dosing) (OS HR 0.56; p=0.03 for weight-based; vs HR 0.89; p=0.54 for fixed dosing). In multivariable analysis, BMI was not associated with PFS or OS. However, the interaction of BMI≥25 and weight-based dosing had a trend toward association with PFS (HR 0.53; 95% CI 0.26 to 1.10; p=0.09) and was associated with OS (HR 0.50; 95% CI 0.25 to 0.99; p=0.05). Patients with BMI<25 tended to have better outcomes with fixed-dose compared with weight-based ICI, while patients with BMI≥25 tended to have better outcomes with weight-based ICI, although these differences did not achieve statistical significance. There was no association between radiographic response and BMI with fixed-dose ICI (p=0.97), but a near-significant trend with weight-based ICI (p=0.1). In subset analyses, the association between BMI, ICI dosing strategy, and clinical outcomes appeared limited to men.ConclusionsThe clinical benefit of ICI in high-BMI populations appears limited to individuals receiving weight-based ICI dosing. Further research into optimal ICI dosing strategies may be warranted.

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Treatment-associated Fatigue in Cancer Patients Treated with Immune Checkpoint Inhibitors; a Systematic Review and Meta-analysis

Clinical Oncology ◽

10.1016/j.clon.2016.06.008 ◽

2016 ◽

Vol 28 (10) ◽

pp. e127-e138 ◽

Cited By ~ 25

Author(s):

O. Abdel-Rahman ◽

D. Helbling ◽

J. Schmidt ◽

U. Petrausch ◽

A. Giryes ◽

...

Keyword(s):

Systematic Review ◽

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis

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191. The impact of antibiotic use on clinical outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.235 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S101-S101

Author(s):

Maria Tsikala Vafea ◽

Neel Belani ◽

Kendra Vieira ◽

Dimitrios Farmakiotis

Keyword(s):

Cancer Patients ◽

Clinical Outcomes ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Progression Free Survival ◽

Antibiotic Use ◽

Experimental Models ◽

The Impact

Abstract Background Observational studies and experimental models suggest that use of antibiotics close to the administration of immune checkpoint inhibitors (ICI) can negatively affect tumor response and patient survival. This observation may be attributed to microbiome dysbiosis and the resultant suppression of host immune response against neoplastic cells. Methods We conducted a systematic search of PUBMED and EMBASE databases and references of articles retrieved. We included studies published between 1/1/17 and 2/1/20, which evaluated the association between antibiotic use and clinical outcomes in cancer patients treated with ICI. Primary endpoints were overall survival (OS), progression free survival (PFS), response rate (RR) and progressive disease (PD) rate. We performed a study-level random-effects meta-analysis with pooling of hazards ratios (HR) for OS, PFS, and odds ratios (OR) for RR and PD (PROSPERO ID: CRD42020166473). Results We included 41 studies with a total of 10,857 patients. The most common malignancies were lung cancer (59.7%), melanoma (23.1%), renal cell and urothelial carcinomas (8.1%). OS and PFS were shorter, RR lower, and PD higher in patients receiving antibiotics, both in univariate analyses and after adjustment for other confounders. Heterogeneity was significant for all outcomes, less so for adjusted OS and PFS (Table). To our knowledge, this is the largest meta-analysis on the association between antibiotic use and efficacy of ICI, and the only one to address RR and PD to-date. Association between antibiotics and clinical outcomes. Conclusion We demonstrated a significant association between antibiotic use and unfavorable clinical outcomes in patients with cancer receiving ICI. Such patients may be an important target group for antibiotic stewardship interventions. The high heterogeneity across all outcomes underscores the need for more detailed, patient-level studies with stratification by host, antibacterial and cancer treatment factors. Disclosures All Authors: No reported disclosures

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Antibiotic use is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2021.03.063 ◽

2021 ◽

Author(s):

Maria Tsikala-Vafea ◽

Neel Belani ◽

Kendra Vieira ◽

Hina Khan ◽

Dimitrios Farmakiotis

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Antibiotic Use ◽

Patients With Cancer

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Association between Body Mass Index and Immune-Related Adverse Events (irAEs) among Advanced-Stage Cancer Patients Receiving Immune Checkpoint Inhibitors: A Pan-Cancer Analysis

Cancers ◽

10.3390/cancers13236109 ◽

2021 ◽

Vol 13 (23) ◽

pp. 6109

Author(s):

Dongyu Zhang ◽

Neil J. Shah ◽

Michael Cook ◽

Matthew Blackburn ◽

Michael T. Serzan ◽

...

Keyword(s):

Body Mass Index ◽

Logistic Regression ◽

Adverse Events ◽

Cancer Patients ◽

Body Mass ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Multivariable Logistic Regression Model ◽

Multivariable Logistic Regression

Evidence regarding the association between body mass index (BMI) and immune-related adverse events (irAEs) among cancer patients receiving immune checkpoint inhibitors (ICIs) is limited. Here, we use cross-sectional hospital-based data to explore their relationship. Pre-treatment BMI was treated as an ordinal variable (<25, 25 to ≤30, ≥30 kg/m2). The outcome of interest was irAEs after ICI initiation. A multivariable logistic regression model estimated the adjusted odds ratio (aOR) and 95% confidence interval (CI) of BMI. A total of 684 patients with stage III or IV cancer were included in the study (lung: 269, melanoma: 204, other: 211). The mean age at the first dose of ICI was 64.1 years (SD = 13.5), 394 patients (57.6%) were male, and over one-third (N = 260, 38.0%) were non-White. Overall, 52.9% of patients had BMI ≥ 25 kg/m2 (25 to ≤30: 217, ≥30: 145) and 288 (42.1%) had irAEs after ICI treatment. Patients with higher BMI tended to have a higher rate of irAEs (<25: 35.7%, 25 to ≤30: 47.0%, ≥30: 49.0%). The multivariable logistic regression yielded consistent results (BMI ≥ 30 vs. BMI < 25: aOR = 1.47, 95% CI = 0.96–2.23; 25 ≤ BMI < 30 vs. BMI < 25: aOR = 1.46, 95% CI = 1.02–2.11, p-trend = 0.04). In conclusion, among patients with advanced cancer receiving ICIs, the rate of irAEs appears to be higher among those with higher BMI.

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Impact of corticosteroids use on efficacy of immune checkpoint inhibitors in cancer patients: A meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15234 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15234-e15234

Author(s):

Jiarui Li ◽

Kaili Yang ◽

Lin Zhao ◽

Chunmei Bai ◽

Zhao Sun

Keyword(s):

Cancer Patients ◽

Clinical Outcomes ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Progression Free Survival ◽

Study Selection ◽

The Impact ◽

Detrimental Impact

e15234 Background: Corticosteroids are commonly used for management of cancer-related symptoms or immune-related adverse events (irAEs) in cancer patients treated with immune checkpoint inhibitors (ICIs). However, given the inhibitory effects of corticosteroids on a broad range of immune responses, it is presumed that the use of these agents may affect the clinical outcomes of ICIs. This meta-analysis aims to explore the impact of corticosteroids use on the efficacy of ICIs in cancer patients. Methods: We conducted a search covering electronic databases (MEDLINE, EMBASE, and CENTRAL), conference abstracts (ASCO and ESMO) and reference lists to identify relevant studies. Studies that reported clinical outcomes of patients with corticosteroids administration before and/or after the initiation of ICIs treatment were eligible for evaluation. The primary outcomes included progression-free survival (PFS) and overall survival (OS). The random-effects model was utilized to synthesize the effect sizes of individual studies. Results: The initial literature search identified 1,900 records. After study selection, a total of 15 studies with 14,123 patients were included in the quantitative analysis. Corticosteroids use significantly reduced PFS (HR = 1.84; 95% CI: 1.30–2.61; P = 0.001) and OS (HR = 1.41; 95% CI: 1.18–1.68; P < 0.001) in cancer patients treated with ICIs. In subgroup analysis, corticosteroids use for cancer-related symptoms was associated with a shorter PFS (HR = 1.98; 95% CI: 1.40–2.78; P < 0.001) and OS (HR = 1.88; 95% CI: 1.25–2.83; P = 0.003), but their use for irAEs did not show a detrimental impact on OS (HR = 1.05; 95% CI: 0.77–1.44; P = 0.740). Conclusions: This meta-analysis indicated that corticosteroids use might hinder the efficacy of ICIs in cancer patients. The indications of corticosteroids use should be strictly controlled during the course of immunotherapy.

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