The negative impact of opioids on cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Ju, Mingguang; Gao, Zhiqiang; Liu, Xiaofang; Zhou, Hu; Wang, Ruiying; Zheng, Chen; Dong, Dao-Song; Zhu, Zhigang; Liu, Cai-Gang

doi:10.1007/s00432-022-04513-0

Cited by 11 publications

(5 citation statements)

References 39 publications

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“…Our findings reveal a noteworthy association between OA treatment and significantly reduced PFS and OS in cancer patients receiving ICI therapy. Consistent with previous research hinting at the potential negative influence of opioids, our results highlight that the impact of opioids varies by tumor type, suggesting a need for tumor-specific strategies in clinical practice [ 6 – 9 ]. The relationship between an ECOG PS of 1 or higher and reduced OS, elevated LDH levels above the normal range, and reduced PFS and OS suggests an association between increasing disease burden and OA usage, which may be related to a worse prognosis.…”

Section: Discussionsupporting

confidence: 89%

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Impact of opioid analgesics on survival in cancer patients receiving immune checkpoint inhibitors

Kavgaci,

Guven,

Kaygusuz

et al. 2024

Support Care Cancer

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Purpose This study aimed to assess the effects of concurrent opioid analgesic (OA) use with immune checkpoint inhibitors (ICIs) on progression-free survival (PFS) and overall survival (OS). Methods In this observational retrospective study, we included advanced cancer patients who received ICIs at Hacettepe University Hospital’s Department of Medical Oncology between June 2018 and January 2023. Results Our study included 375 recurrent or metastatic cancer patients treated with ICIs in the first, second line, or beyond. There were no significant differences between the OA-treated and OA-untreated groups regarding median age, age group, gender, primary tumor location, ICI type, or the presence of baseline liver and lung metastases. However, the OA-treated group exhibited a significantly higher proportion of patients who had received three or more prior treatments before initiating ICIs (p = 0.015). OA-Untreatment was significantly correlated with prolonged mPFS (6.83 vs. 4.30 months, HR 0.59, 95% CI 0.44–0.79, p < 0.001) and mOS (17.05 vs. 7.68 months, HR 0.60, 95% CI 0.45–0.80, p < 0.001). Conclusions Our study demonstrates an association between the concurrent use of OAs and reduced OS and PFS in patients treated with ICIs. While OA treatment serves as a surrogate marker for higher disease burden, it may also suggest a potential biological relationship between opioids and immunotherapy efficacy.

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Section: Discussionsupporting

confidence: 89%

“…Furthermore, OAs can disturb the composition of the intestinal microbiota and increase the presence of regulatory T cells (Tregs), resulting in impairment of the immune system. Retrospective cohort studies have indicated that the use of OAs may correlate with less favorable prognoses among patients treated with ICIs [ 6 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of opioid analgesics on survival in cancer patients receiving immune checkpoint inhibitors

Kavgaci,

Guven,

Kaygusuz

et al. 2024

Support Care Cancer

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“…However, not all solid tumors are sensitive to immunotherapy. The use of opioids is detrimental to survival outcomes for cancer patients receiving anti-PD-1/PD-L1 therapies ( 27 ). Two multicenter retrospective studies about solid cancers revealed that opioids used during immunotherapy were associated with a higher risk of early progression ( 28 , 29 ), and shorter OS ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Mu opioid receptor mRNA overexpression predicts poor prognosis among 18 common solid cancers: A pan-cancer analysis

et al. 2023

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BackgroundOpioids are widely used for patients with solid tumors during surgery and for cancer pain relief. We conducted a pan-cancer genomic analysis to investigate the prognostic features of Mu opioid receptor (MOR) mRNA expression across 18 primary solid cancers.MethodsAll the data of cancer with MOR mRNA were retrieved from cBioPortal for Cancer Genomics. Logistic regression was used to determine the associations between MOR mRNA expression and clinicopathological features. Log-rank test and Cox regression was used for survival analysis. Subgroup analysis and propensity score matching were also carried out.Results7,274 patients, including 1,112 patients with positive MOR mRNA expression, were included for data analyses. Positive MOR mRNA expression was associated with more advanced stage of T (adjusted Odds ratio [OR], 1.176; 95% confidence interval [CI], 1.022-1.354; P=0.024), M (adjusted OR, 1.548; 95% CI, 1.095-2.189; P=0.013) except N (adjusted OR, 1.145; 95% CI, 0.975-1.346; P=0.101), and worse prognosis for overall survival (Hazard ratio [HR] 1.347, 95% CI 1.200-1.512, P<0.001), progression-free survival (HR 1.359, 95% CI 1.220-1.513, P<0.001), disease-free survival (HR 1.269, 95% CI 1.016-1.585, P<0.001) and disease-specific survival (HR 1.474, 95% CI 1.284-1.693, P<0.001). Patients with positive MOR mRNA expression tended to be classified as tumor microenvironment immune types II, representing low PD-L1 and low CD8A expression.ConclusionMOR mRNA overexpression is associated with poor prognosis and poor response to PD-L1 therapy.

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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%

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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The negative impact of opioids on cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Cited by 11 publications

References 39 publications

Impact of opioid analgesics on survival in cancer patients receiving immune checkpoint inhibitors

Impact of opioid analgesics on survival in cancer patients receiving immune checkpoint inhibitors

Mu opioid receptor mRNA overexpression predicts poor prognosis among 18 common solid cancers: A pan-cancer analysis

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

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