Statin use improves the efficacy of nivolumab in patients with advanced renal cell carcinoma

Santoni, Matteo; Massari, Francesco; Matrana, Marc; Basso, Umberto; Giorgi, Ugo De; Aurilio, Gaetano; Buti, Sebastiano; Incorvaia, Lorena; Rizzo, Mimma; Martignetti, Angelo; Maslov, Diana; Tawagi, Karine; Philon, Ernest; Blake, Zoe; Porta, Camillo; Battelli, Nicola

doi:10.1016/j.ejca.2022.04.035

Cited by 10 publications

(8 citation statements)

References 36 publications

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“…The mean ages of the patients were 57 to 67 years, and the proportions of men were 56 to 75%. In ten of the included studies ( 18 – 21 , 24 , 27 – 30 , 32 ), surgeries such as nephrectomy were performed, while in five studies ( 17 , 22 , 25 , 31 , 33 ), non-surgical therapies such as interferon, temsirolimus, Immunotherapy, and target drugs were applied. In 15 of the included studies, statin use was defined as confirmed concurrent use of statin via medical charts at the diagnosis of RCC ( 17 – 25 , 27 , 29 – 33 ), while for the other two studies ( 26 , 28 ), stain use was defined as regular statin use before the diagnosis of RCC.…”

Section: Resultsmentioning

confidence: 99%

“…However, previous studies evaluating the influence of statin on survival of patients with RCC yielded inconsistent results ( 16 ). Some studies suggested that statin use may be associated with improved survival in patients with RCC ( 17 – 25 ), while others did not show consistent results ( 26 – 33 ). Therefore, in this study, we performed a systematic review and meta-analysis to comprehensively investigate the association between statin use and survival outcomes in patients with RCC.…”

Section: Introductionmentioning

confidence: 99%

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Influence of statin use on prognosis of patients with renal cell cancer: a meta-analysis

et al. 2023

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BackgroundStatin may confer anticancer efficacy, while the studies evaluating the influence of statin on survival of patients with renal cell cancer (RCC) yielded inconsistent results. A systematic review and meta-analysis was performed to investigate the association between statin use and survival of patients with RCC.Materials and MethodsCohort studies were identified by search of PubMed, Embase, and Web of Science databases according to the objective of the meta-analysis. A random-effect model incorporating the possible between-study heterogeneity was used for meta-analysis. Subgroup analyses according to study characteristics were also performed.ResultsSeventeen cohort studies involving 42528 patients with RCC were available for the meta-analysis. Results showed that statin use was associated with a better overall survival (OS, hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.65 to 0.84, p < 0.001; I2 = 40%), progression progression-free survival (PFS, HR: 0.82, 95% CI: 0.68 to 0.98, p = 0.03; I2 = 52%), and cancer-specific survival (CSS, HR: 0.76, 95% CI: 0.59 to 0.99, p = 0.04; I2 = 38%). Besides, for the outcome of OS and PFS, subgroup analyses showed similar results in patients with surgical and non-surgical anticancer treatments, and in patients with stage I-III and stage IV RCC (p values for subgroup difference all > 0.05).ConclusionsStatin use may be associated with improved survival outcomes in patients with RCC. Although prospective clinical studies should be considered to validate these results, these findings suggest that statins may be potential adjuvant therapy for patients with RCC.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of statin use on prognosis of patients with renal cell cancer: a meta-analysis

et al. 2023

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“…observed no difference revealed on ORR, PFS, OS or overall clinical benefit in RCC patients with immunotherapy between PPI exposure and PPI absent ( 41 , 42 ). Interestingly, unlike the inhibitory effect of antibiotics, concomitant Statin with ICIs showed a positive effect on advanced RCC patients in the prolonged OS and PFS and higher overall clinical benefit ( 41 , 43 ).…”

Section: Discussionmentioning

confidence: 99%

The negative effect of antibiotics on RCC patients with immunotherapy: A systematic review and meta-analysis

Luo

Hao

et al. 2022

Front. Immunol.

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BackgroundMicrobiome dysbiosis is considered a predictive biomarker of clinical response in renal cell carcinoma (RCC), which can be regulated by antibiotics (ATB). Multiple studies have shown that concomitant ATB administration has inhibitory effects on immunotherapy in RCC. This review aimed to assess the impact of ATB on patient survival and tumor response in RCC with immunotherapy.MethodsLiterature evaluating the effect of ATB on immunotherapy in RCC from Cochrane Library®, PubMed®, Embase®, Scopus®, and Web of Science® were systematically searched. Hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), odds ratio (OR) for objective response rate (ORR) and primary progressive disease (PD) were pooled as effect sizes for clinical outcomes. Subgroup analysis was conducted to reveal the determinants of the effect of ATB on immunotherapy, including time windows of ATB exposure to immunotherapy initiation, ICIs treatment and study location. The leave-one-out approach was adopted to analyze the heterogeneity formulated. Cumulative meta-analysis adding by time was used to observe dynamic changes of the results.ResultsTen studies were included in the systematic review and six studies (with n=1,104 patients) were included in the meta-analysis, four studies were excluded for overlapping patients with subsequent larger studies and lack of unique patient-level data. ATB administration was significantly correlated with shorter PFS (HR=2.10, 95%CI [1.54; 2.85], I2 = 2% after omitting study Derosa et al, 2021 detected by leave-one-out approach), shorter OS (HR=1.69, 95%CI [1.34; 2.12], I2 = 25%) and worse ORR (OR=0.58, 95%CI [0.41; 0.84]), but no difference was observed in risk of PD (OR=1.18, 95%CI [0.97; 1.44]). No significant differences existed among the subgroups for determining the determinants of ATB inhibition.ConclusionsConcomitant ATB with immunotherapy was associated with worse PFS, OS and ORR in RCC. No publication bias was observed in this study.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=349577, identifier CRD42022349577.

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“…For instance, simvastatin treatment, tumor antigen vaccination, and anti-PD-1 blockade showed better tumor control and increased survival rates of B16 and TC-1 tumor models [78]. In clinical studies, the combination of statins with immune checkpoint blockade showed better outcomes in metastatic melanoma, pleural mesothelioma, advanced non-small-cell lung cancer patients, and advanced renal carcinoma [79][80][81].…”

Section: Targeting Cancer Cell Metabolism To Improve Immunotherapy Re...mentioning

confidence: 99%

Immunological Aspects of Cancer Cell Metabolism

Ucche,

Hayakawa

2024

IJMS

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Cancer cells adeptly manipulate their metabolic processes to evade immune detection, a phenomenon intensifying the complexity of cancer progression and therapy. This review delves into the critical role of cancer cell metabolism in the immune-editing landscape, highlighting how metabolic reprogramming facilitates tumor cells to thrive despite immune surveillance pressures. We explore the dynamic interactions within the tumor microenvironment (TME), where cancer cells not only accelerate their glucose and amino acid metabolism but also induce an immunosuppressive state that hampers effective immune response. Recent findings underscore the metabolic competition between tumor and immune cells, particularly focusing on how this interaction influences the efficacy of emerging immunotherapies. By integrating cutting-edge research on the metabolic pathways of cancer cells, such as the Warburg effect and glutamine addiction, we shed light on potential therapeutic targets. The review proposes that disrupting these metabolic pathways could enhance the response to immunotherapy, offering a dual-pronged strategy to combat tumor growth and immune evasion.

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Statin use improves the efficacy of nivolumab in patients with advanced renal cell carcinoma

Cited by 10 publications

References 36 publications

Influence of statin use on prognosis of patients with renal cell cancer: a meta-analysis

Influence of statin use on prognosis of patients with renal cell cancer: a meta-analysis

The negative effect of antibiotics on RCC patients with immunotherapy: A systematic review and meta-analysis

Immunological Aspects of Cancer Cell Metabolism

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