LYU Zhengqin, ZHAO Yuhao, GUO Yuanyuan, LIU Beibei, LIU Jianmin. Research Progress on the Effect of Clinical Concomitant Medication on Efficacy of Immune Checkpoint Inhibitors in Urothelial Carcinoma[J]. Medical Journal of Peking Union Medical College Hospital, 2024, 15(2): 394-399. DOI: 10.12290/xhyxzz.2023-0488
Citation: LYU Zhengqin, ZHAO Yuhao, GUO Yuanyuan, LIU Beibei, LIU Jianmin. Research Progress on the Effect of Clinical Concomitant Medication on Efficacy of Immune Checkpoint Inhibitors in Urothelial Carcinoma[J]. Medical Journal of Peking Union Medical College Hospital, 2024, 15(2): 394-399. DOI: 10.12290/xhyxzz.2023-0488

Research Progress on the Effect of Clinical Concomitant Medication on Efficacy of Immune Checkpoint Inhibitors in Urothelial Carcinoma

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  • Corresponding author:

    LIU Jianmin, E-mail: LIU-join-jm@sina.com

  • Received Date: October 20, 2023
  • Accepted Date: November 02, 2023
  • Available Online: January 02, 2024
  • Issue Publish Date: March 29, 2024
  • Immune checkpoint inhibitors (ICIs) have been approved for the treatment of urothelial carcinoma(UC). However, the use of antibiotics, proton pump inhibitors, corticosteroids, beta-blockers, metformin, and statin concomitant medications in some patients due to complications during the treatment process may affect the clinical efficacy of ICIs through different pathway, making it difficult for patients to derive clinical benefit or making it more likely to develop drug resistance. In this paper, we present a review of the effects of the above concomitant drugs on ICIs in the treatment of patients with advanced UC, with a view to provide reference for the application of individualized treatment strategies of ICIs in patients with advanced UC.
  • [1]
    Kim T K, Herbst R S, Chen L P. Defining and unders-tanding adaptive resistance in cancer immunotherapy[J]. Trends Immunol, 2018, 39(8): 624-631. DOI: 10.1016/j.it.2018.05.001
    [2]
    Hopkins A M, Kichenadasse G, Karapetis C S, et al. Concomitant antibiotic use and survival in urothelial carcinoma treated with atezolizumab[J]. Eur Urol, 2020, 78(4): 540-543. DOI: 10.1016/j.eururo.2020.06.061
    [3]
    Lopes S, Pabst L, Dory A, et al. Do proton pump inhibitors alter the response to immune checkpoint inhibitors in cancer patients? A meta-analysis[J]. Front Immunol, 2023, 14: 1070076. DOI: 10.3389/fimmu.2023.1070076
    [4]
    Drakaki A, Dhillon P K, Wakelee H, et al. Association of baseline systemic corticosteroid use with overall survival and time to next treatment in patients receiving immune check-point inhibitor therapy in real-world US oncology practice for advanced non-small cell lung cancer, melanoma, or urothelial carcinoma[J]. Oncoimmunology, 2020, 9(1): 1824645. DOI: 10.1080/2162402X.2020.1824645
    [5]
    Kokolus K M, Zhang Y, Sivik J M, et al. Beta blocker use correlates with better overall survival in metastatic melanoma patients and improves the efficacy of immunotherapies in mice[J]. Oncoimmunology, 2018, 7(3): e1405205. DOI: 10.1080/2162402X.2017.1405205
    [6]
    Fiala O, Buti S, Takeshita H, et al. Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study[J]. Cancer Immunol Immunother, 2023, 72(11): 3665-3682. DOI: 10.1007/s00262-023-03518-z
    [7]
    Weersma R K, Zhernakova A, Fu J Y. Interaction between drugs and the gut microbiome[J]. Gut, 2020, 69(8): 1510-1519. DOI: 10.1136/gutjnl-2019-320204
    [8]
    Matson V, Fessler J, Bao R Y, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients[J]. Science, 2018, 359(6371): 104-108. DOI: 10.1126/science.aao3290
    [9]
    Ubeda C, Pamer E G. Antibiotics, microbiota, and immune defense[J]. Trends Immunol, 2012, 33(9): 459-466. DOI: 10.1016/j.it.2012.05.003
    [10]
    Tsikala-Vafea M, Belani N, Vieira K, et al. Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis[J]. Int J Infect Dis, 2021, 106: 142-154. DOI: 10.1016/j.ijid.2021.03.063
    [11]
    Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J]. Science, 2018, 359(6371): 91-97. DOI: 10.1126/science.aan3706
    [12]
    Wu Q, Liu J J, Wu S M, et al. The impact of antibiotics on efficacy of immune checkpoint inhibitors in malignancies: a study based on 44 cohorts[J]. Int Immunopharmacol, 2021, 92: 107303. DOI: 10.1016/j.intimp.2020.107303
    [13]
    Sivan A, Corrales L, Hubert N, et al. Commensal Bifido-bacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J]. Science, 2015, 350(6264): 1084-1089. DOI: 10.1126/science.aac4255
    [14]
    Matson V, Fessler J, Bao R, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients[J]. Science, 2018, 359(6371): 104-108. DOI: 10.1126/science.aao3290
    [15]
    Casadei C, Lolli C, Farolfi A. Immune-checkpoint inhibitors and the importance of concomitant medications: focus on antibiotics[J]. Ann Transl Med, 2019, 7(Suppl 8): S339.
    [16]
    Rosa R G, Goldani L Z, Dos Santos R P. Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropaenia: a prospective cohort study[J]. BMC Infect Dis, 2014, 14: 286. DOI: 10.1186/1471-2334-14-286
    [17]
    Routy B, Gopalakrishnan V, Daillère R, et al. The gut microbiota influences anticancer immunosurveillance and general health[J]. Nat Rev Clin Oncol, 2018, 15(6): 382-396. DOI: 10.1038/s41571-018-0006-2
    [18]
    Esteves M, Rollason V, Grosgurin O. Proton pump inhibi-tors overprescription[J]. Rev Med Suisse, 2017, 13(579): 1782-1786.
    [19]
    Reveles K R, Ryan C N, Chan L, et al. Proton pump inhibitor use associated with changes in gut microbiota composition[J]. Gut, 2018, 67(7): 1369-1370. DOI: 10.1136/gutjnl-2017-315306
    [20]
    Hojo M, Asahara T, Nagahara A, et al. Gut microbiota composition before and after use of proton pump inhibitors[J]. Dig Dis Sci, 2018, 63(11): 2940-2949. DOI: 10.1007/s10620-018-5122-4
    [21]
    Hopkins A M, Kichenadasse G, Karapetis C S, et al. Concomitant proton pump inhibitor use and survival in urothelial carcinoma treated with atezolizumab[J]. Clin Cancer Res, 2020, 26(20): 5487-5493. DOI: 10.1158/1078-0432.CCR-20-1876
    [22]
    Zhang L L, Chen C, Chai D Q, et al. Effects of PPIs use on clinical outcomes of urothelial cancer patients receiving immune checkpoint inhibitor therapy[J]. Front Pharmacol, 2022, 13: 1018411. DOI: 10.3389/fphar.2022.1018411
    [23]
    Rizzo A, Santoni M, Mollica V, et al. The impact of concomitant proton pump inhibitors on immunotherapy efficacy among patients with urothelial carcinoma: a meta-analysis[J]. J Pers Med, 2022, 12(5): 842. DOI: 10.3390/jpm12050842
    [24]
    Okuyama Y, Hatakeyama S, Numakura K, et al. Prognostic impact of proton pump inhibitors for immunotherapy in advanced urothelial carcinoma[J]. BJUI Compass, 2022, 3(2): 154-161. DOI: 10.1002/bco2.118
    [25]
    Kunimitsu Y, Morio K, Hirata S, et al. Effects of proton pump inhibitors on survival outcomes in patients with metastatic or unresectable urothelial carcinoma treated with pembrolizumab[J]. Biol Pharm Bull, 2022, 45(5): 590-595. DOI: 10.1248/bpb.b21-00939
    [26]
    Gong J, Chehrazi-Raffle A, Placencio-Hickok V, et al. The gut microbiome and response to immune checkpoint inhibi-tors: preclinical and clinical strategies[J]. Clin Transl Med, 2019, 8(1): 9. DOI: 10.1186/s40169-019-0225-x
    [27]
    Gopalakrishnan V, Spencer C N, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients[J]. Science, 2018, 359(6371): 97-103. DOI: 10.1126/science.aan4236
    [28]
    Laheij R J F, Sturkenboom M C J M, Hassing R J, et al. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs[J]. JAMA, 2004, 292(16): 1955-1960. DOI: 10.1001/jama.292.16.1955
    [29]
    Skribek M, Rounis K, Afshar S, et al. Effect of corticosteroids on the outcome of patients with advanced non-small cell lung cancer treated with immune-checkpoint inhibitors[J]. Eur J Cancer, 2021, 145: 245-254. DOI: 10.1016/j.ejca.2020.12.012
    [30]
    Petrelli F, Signorelli D, Ghidini M, et al. Association of steroids use with survival in patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis[J]. Cancers (Basel), 2020, 12(3): 546. DOI: 10.3390/cancers12030546
    [31]
    Chen C Y, Rao S S, Yue T, et al. Glucocorticoid-induced loss of beneficial gut bacterial extracellular vesicles is associated with the pathogenesis of osteonecrosis[J]. Sci Adv, 2022, 8(15): eabg8335. DOI: 10.1126/sciadv.abg8335
    [32]
    Fucà G, Galli G, Poggi M, et al. Modulation of peripheral blood immune cells by early use of steroids and its associa-tion with clinical outcomes in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors[J]. ESMO Open, 2019, 4(1): e000457. DOI: 10.1136/esmoopen-2018-000457
    [33]
    Spakowicz D, Hoyd R, Muniak M, et al. Inferring the role of the microbiome on survival in patients treated with immune checkpoint inhibitors: causal modeling, timing, and classes of concomitant medications[J]. BMC Cancer, 2020, 20(1): 383. DOI: 10.1186/s12885-020-06882-6
    [34]
    Ricciuti B, Dahlberg S E, Adeni A, et al. Immune checkpoint inhibitor outcomes for patients with non-small-cell lung cancer receiving baseline corticosteroids for palliative versus nonpalliative indications[J]. J Clin Oncol, 2019, 37(22): 1927-1934. DOI: 10.1200/JCO.19.00189
    [35]
    Horvat T Z, Adel N G, Dang T O, et al. Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at memorial sloan kettering cancer center[J]. J Clin Oncol, 2015, 33(28): 3193-3198. DOI: 10.1200/JCO.2015.60.8448
    [36]
    Robesti D, Nocera L, Belladelli F, et al. The immune-related adverse events paradox in locally advanced or metastatic urothelial cancer after atezolizumab immunotherapy: analysis of individual patient data from IMvigor210 and IMvigor211 trials[J]. BJU Int, 2024, 133(2): 158-168. DOI: 10.1111/bju.16121
    [37]
    Maxwell R, Luksik A S, Garzon-Muvdi T, et al. Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nerv-ous system[J]. Oncoimmunology, 2018, 7(12): e1500108. DOI: 10.1080/2162402X.2018.1500108
    [38]
    Oh M S, Guzner A, Wainwright D A, et al. The impact of beta blockers on survival outcomes in patients with non-small-cell lung cancer treated with immune checkpoint inhibitors[J]. Clin Lung Cancer, 2021, 22(1): e57-e62. DOI: 10.1016/j.cllc.2020.07.016
    [39]
    Bucsek M J, Qiao G X, MacDonald C R, et al. β-adren-ergic signaling in mice housed at standard temperatures suppresses an effector phenotype in CD8+ T cells and under-mines checkpoint inhibitor therapy[J]. Cancer Res, 2017, 77(20): 5639-5651. DOI: 10.1158/0008-5472.CAN-17-0546
    [40]
    Mellgard G, Patel V G, Zhong X B, et al. Effect of concurrent beta-blocker use in patients receiving immune check-point inhibitors for advanced solid tumors[J]. J Cancer Res Clin Oncol, 2023, 149(7): 2833-2841. DOI: 10.1007/s00432-022-04159-y
    [41]
    Rains S L, Amaya C N, Bryan B A. Beta-adrenergic receptors are expressed across diverse cancers[J]. Oncoscience, 2017, 4(7/8): 95-105.
    [42]
    Udumyan R, Botteri E, Jerlstrom T, et al. Beta-blocker use and urothelial bladder cancer survival: a Swedish register-based cohort study[J]. Acta Oncol, 2022, 61(8): 922-930. DOI: 10.1080/0284186X.2022.2101902
    [43]
    Scharping N E, Menk A V, Whetstone R D, et al. Efficacy of PD-1 blockade is potentiated by metformin-induced reduction of tumor hypoxia[J]. Cancer Immunol Res, 2017, 5(1): 9-16. DOI: 10.1158/2326-6066.CIR-16-0103
    [44]
    Gandhi S, Pandey M, Ammannagari N, et al. Impact of concomitant medication use and immune-related adverse events on response to immune checkpoint inhibitors[J]. Immunotherapy, 2020, 12(2): 141-149. DOI: 10.2217/imt-2019-0064
    [45]
    Afzal M Z, Mercado R R, Shirai K. Efficacy of metformin in combination with immune checkpoint inhibitors (anti-PD-1/anti-CTLA-4) in metastatic malignant melanoma[J]. J Immunother Cancer, 2018, 6(1): 64. DOI: 10.1186/s40425-018-0375-1
    [46]
    Wu H, Esteve E, Tremaroli V, et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug[J]. Nat Med, 2017, 23(7): 850-858. DOI: 10.1038/nm.4345
    [47]
    Liu W H, Wang Y, Luo J Q, et al. Pleiotropic effects of metformin on the antitumor efficiency of immune checkpoint inhibitors[J]. Front Immunol, 2020, 11: 586760.
    [48]
    Zhang J J, Zhang Q S, Li Z Q, et al. Metformin attenuates PD-L1 expression through activating Hippo signaling pathway in colorectal cancer cells[J]. Am J Transl Res, 2019, 11(11): 6965-6976.
    [49]
    Kim H, Seol Y M, Choi Y J, et al. HMG CoA reductase expression as a prognostic factor in Korean patients with breast cancer: A retrospective study[J]. Medicine (Baltimore), 2019, 98(13): e14968. DOI: 10.1097/MD.0000000000014968
    [50]
    Cantini L, Pecci F, Hurkmans D, et al. Statin treatment improves response to anti-PD1 agents in patients with malignant pleural mesothelioma and non-small cell lung cancer[J]. J Clin Oncol, 2020, 38(15_suppl): 3074. DOI: 10.1200/JCO.2020.38.15_suppl.3074
    [51]
    Cantini L, Pecci F, Hurkmans D P, et al. High-intensity statins are associated with improved clinical activity of PD-1 inhibitors in malignant pleural mesothelioma and advanced non-small cell lung cancer patients[J]. Eur J Cancer, 2021, 144: 41-48. DOI: 10.1016/j.ejca.2020.10.031
    [52]
    Choe E J, Lee C H, Bae J H, et al. Atorvastatin enhances the efficacy of immune checkpoint therapy and suppresses the cellular and extracellular vesicle PD-L1[J]. Pharmaceutics, 2022, 14(8): 1660. DOI: 10.3390/pharmaceutics14081660
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