Concomitant Statins and the Survival of Patients with Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Meta-Analysis

Zhang, Lei; Wang, Hong; Tian, Jizheng; Sui, Lili; Chen, Xiaoyan

doi:10.1155/2022/3429462

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…Table 1 summarizes the basic characteristics of the 23 included publications (10)(11)(12)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). These publications were from China (n=19), the United States of America (n=2), Australia (n=1), and France (n=1).…”

Section: Basic Characteristicsmentioning

confidence: 99%

“…Notably, besides the negative impact on ICIs efficacy, some concomitant medications (e.g., statins, metformin, b-blockers, and probiotics) may exert an enhancing effect on ICIs efficacy; however, the level of evidence remains poor and controversial (12). In recent years, the number of meta-analyses focusing on the impact of concomitant medications has surged.…”

Section: Introductionmentioning

confidence: 99%

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Impact of concomitant medications on the efficacy of immune checkpoint inhibitors: an umbrella review

Li,

Zhang,

Yang

et al. 2023

Front. Immunol.

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IntroductionCancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs can be influenced by various factors, including the use of concomitant medications.MethodsWe searched databases (PubMed, Embase, Cochrane Library, Web of Science) for systematic reviews and meta-analyses for systematic reviews and meta-analyses on the impact of concomitant medications on ICIs efficacy, published from inception to January 1, 2023. We evaluated the methodological quality of the included meta-analyses, and re-synthesized data using a random-effects model and evidence stratification.ResultsWe included 23 publications, comprising 11 concomitant medications and 112 associations. Class II-IV evidence suggested that antibiotics have a negative impact on ICIs efficacy. However, ICIs efficacy against melanoma, hepatocellular carcinoma, and esophageal squamous cell carcinoma was not affected, this effect was related to the exposure window (class IV). Class III evidence suggested that proton pump inhibitors have a negative impact on ICIs efficacy; nevertheless, the efficacy against melanoma and renal cell carcinoma was not affected, and the effect was related to exposure before the initiation of ICIs therapy (class II). Although class II/III evidence suggested that steroids have a negative impact, this effect was not observed when used for non-cancer indications and immune-related adverse events (class IV). Class IV evidence suggested that opioids reduce ICIs efficacy, whereas statins and probiotics may improve ICIs efficacy. ICIs efficacy was not affected by histamine 2 receptor antagonists, aspirin, metformin, β-blockers, and nonsteroidal anti-inflammatory agents.ConclusionCurrent evidence suggests that the use of antibiotics, PPIs, steroids, and opioids has a negative impact on the efficacy of ICIs. However, this effect may vary depending on the type of tumor, the timing of exposure, and the intended application. Weak evidence suggests that statins and probiotics may enhance the efficacy of ICIs. Aspirin, metformin, β-blockers, and NSAIDs do not appear to affect the efficacy of ICIs. However, caution is advised in interpreting these results due to methodological limitations.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO,identifier, CRD42022328681.

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Section: Basic Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of concomitant medications on the efficacy of immune checkpoint inhibitors: an umbrella review

Li,

Zhang,

Yang

et al. 2023

Front. Immunol.

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Immune Checkpoint Inhibitors and the Exposome: Host-Extrinsic Factors Determine Response, Survival, and Toxicity

et al. 2023

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Cancer immunotherapy, largely represented by immune checkpoint inhibitors (ICIs), has led to substantial changes in preclinical cancer research and clinical oncology practice over the past decade. However, the efficacy and toxicity profiles of ICIs remain highly variable among patients, with only a fraction achieving a significant benefit. New combination therapeutic strategies are being investigated, and the search for novel predictive biomarkers is ongoing, mainly focusing on tumor- and host-intrinsic components. Less attention has been directed to all the external, potentially modifiable factors that compose the exposome, including diet and lifestyle, infections, vaccinations, and concomitant medications, which could affect the immune system response and its activity against cancer cells. We hereby provide a review of the available clinical evidence elucidating the impact of host-extrinsic factors on ICI response and toxicity.

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Comedications with Immune Checkpoint Inhibitors: Involvement of the Microbiota, Impact on Efficacy and Practical Implications

Colard-Thomas

Thomas

Viala

2023

Cancers

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Immune checkpoint inhibitors (ICIs) have been a major breakthrough in solid oncology over the past decade. The immune system and the gut microbiota are involved in their complex mechanisms of action. However, drug interactions have been suspected of disrupting the fine equilibrium necessary for optimal ICI efficacy. Thus, clinicians are facing a great deal of sometimes contradictory information on comedications with ICIs and must at times oppose conflicting objectives between oncological response and comorbidities or complications. We compiled in this review published data on the role of the microbiota in ICI efficacy and the impact of comedications. We found mostly concordant results on detrimental action of concurrent corticosteroids, antibiotics, and proton pump inhibitors. The timeframe seems to be an important variable each time to preserve an initial immune priming at ICIs initiation. Other molecules have been associated with improved or impaired ICIs outcomes in pre-clinical models with discordant conclusions in retrospective clinical studies. We gathered the results of the main studies concerning metformin, aspirin, and non-steroidal anti-inflammatory drugs, beta blockers, renin-angiotensin-aldosterone system inhibitors, opioids, and statins. In conclusion, one should always assess the necessity of concomitant treatment according to evidence-based recommendations and discuss the possibility of postponing ICI initiation or switching strategies to preserve the critical window.

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Concomitant Statins and the Survival of Patients with Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Meta-Analysis

Cited by 3 publications

References 40 publications

Impact of concomitant medications on the efficacy of immune checkpoint inhibitors: an umbrella review

Impact of concomitant medications on the efficacy of immune checkpoint inhibitors: an umbrella review

Immune Checkpoint Inhibitors and the Exposome: Host-Extrinsic Factors Determine Response, Survival, and Toxicity

Comedications with Immune Checkpoint Inhibitors: Involvement of the Microbiota, Impact on Efficacy and Practical Implications

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