Integrated analysis of concomitant medications and oncological outcomes from PD-1/PD-L1 checkpoint inhibitors in clinical practice
Open accessAbstract
Background: Concomitant medications, such as steroids, proton pump inhibitors (PPI) and antibiotics, might affect clinical outcomes with immune checkpoint inhibitors. Methods: We conducted a multicenter observational retrospective study aimed at evaluating the impact of concomitant medications on clinical outcomes, by weighing their associations with baseline clinical characteristics (including performance status, burden of disease and body mass index) and the underlying causes for their prescription. This analysis included consecutive stage IV patients with cancer, who underwent treatment with single agent antiprogrammed death-1/programmed death ligand-1 (PD-1/PD-L1) with standard doses and schedules at the medical oncology departments of 20 Italian institutions. Each medication taken at the immunotherapy initiation was screened and collected into key categories as follows: corticosteroids, antibiotics, gastric acid suppressants (including proton pump inhibitors - PPIs), statins and other lipid-lowering agents, aspirin, anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors/Angiotensin II receptor blockers, calcium antagonists, β-blockers, metformin and other oral antidiabetics, opioids. Results: From June 2014 to March 2020, 1012 patients were included in the analysis. Primary tumors were: non-small cell lung cancer (52.2%), melanoma (26%), renal cell carcinoma (18.3%) and others (3.6%). Baseline statins (HR 1.60 (95% CI 1.14 to 2.25), p=0.0064), aspirin (HR 1.47 (95% CI 1.04 to 2.08, p=0.0267) and β-blockers (HR 1.76 (95% CI 1.16 to 2.69), p=0.0080) were confirmed to be independently related to an increased objective response rate. Patients receiving cancer-related steroids (HR 1.72 (95% CI 1.43 to 2.07), p<0.0001), prophylactic systemic antibiotics (HR 1.85 (95% CI 1.23 to 2.78), p=0.0030), prophylactic gastric acid suppressants (HR 1.29 (95% CI 1.09 to 1.53), p=0.0021), PPIs (HR 1.26 (95% CI 1.07 to 1.48), p=0.0050), anticoagulants (HR 1.43 (95% CI: 1.16 to 1.77), p=0.0007) and opioids (HR 1.71 (95% CI 1.28 to 2.28), p=0.0002) were confirmed to have a significantly higher risk of disease progression. Patients receiving cancer-related steroids (HR 2.16 (95% CI 1.76 to 2.65), p<0.0001), prophylactic systemic antibiotics (HR 1.93 (95% CI 1.25 to 2.98), p=0.0030), prophylactic gastric acid suppressants (HR 1.29 (95% CI 1.06 to 1.57), p=0.0091), PPI (HR 1.26 (95% CI 1.04 to 1.52), p=0.0172), anticoagulants (HR 1.45 (95% CI 1.14 to 1.84), p=0.0024) and opioids (HR 1.53 (95% CI 1.11 to 2.11), p=0.0098) were confirmed to have a significantly higher risk of death. Conclusion: We confirmed the association between baseline steroids administered for cancer-related indication, systemic antibiotics, PPIs and worse clinical outcomes with PD-1/PD-L1 checkpoint inhibitors, which can be assumed to have immune-modulating detrimental effects.
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PPI use is connected to fecal microbiota oralization and worse anti-PD-1 outcomes.
“As previously reported, they also link PPI use with fecal microbiota oralization32 and adverse outcomes in response to anti-PD-1 therapy33.”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [33]
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“Finally, 41 publications were eligible and were included in the meta-analysis (17, 18, 19; 20, 21, 10, 22-25, 26; 27-38, 39; 40-43, 44; 45-55, 13).”
Zhang, Y., Chen, H., Chen, S., Li, Z., Chen, J., & Li, W. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1957605 · Cited by 70 · see citing works
“Sensitivity analyses revealed that no individual study could substantially affect the pooled HRs of OS, whereas the pooled HRs of PFS were influenced significantly by removal of the studies by Cortellini et al. 202018 or Nichetti et al. 2020,22 thereby suggesting that pooled results were not robust or stable (Suppleme…”
BackgroundInfluentialCortellini, A., Ricciuti, B., Facchinetti, F., Alessi, J. V., Venkatraman, D., Dall’Olio, F. G., Cravero, P., Vaz, V. R., Ottaviani, D., Majem, M., et al. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2021.08.1744 · Cited by 67 · see citing works
Self-citationKawada-Horitani, E., Kita, S., Okita, T., Nakamura, Y., Nishida, H., Honma, Y., Fukuda, S., Tsugawa-Shimizu, Y., Kozawa, J., Sakaue, T., et al. (2022) · Diabetologia · doi:10.1007/s00125-022-05708-3 · Cited by 69 · see citing works
“Nonselective immunosuppressants such as steroids may counteract the cancer immunotherapy itself and have been reported to result in worse outcomes [34, 35].”
BackgroundJennings, M. R., Munn, D. H., & Blazeck, J. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003013 · Cited by 63 · see citing works
Poels, K., Neppelenbroek, S. I. M., Kersten, M. J., Antoni, M. L., Lutgens, E., & Seijkens, T. T. P. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002916 · Cited by 63 · see citing works
Novel Immunotherapies for Osteosarcoma
Lu, Y., Zhang, J., Chen, Y., Kang, Y., Liao, Z., He, Y., & Zhang, C. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.830546 · Cited by 56 · see citing works
“suggested that concomitant medication of a PD-1/ PD-L1 ICI with prednisone can worsen patients’ORR, PFS, and OS (113, 114).”
BackgroundPinato, D. J., Li, X., Mishra-Kalyani, P. S., D’Alessio, A., Fulgenzi, C. A. M., Scheiner, B., Pinter, M., Wei, G., Schneider, J., Rivera, D. R. R., et al. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100747 · Cited by 55 · see citing works
“[16] Cortellini A, Tucci M, Adamo V, Stucci LS, Russo A, Tanda ET, et al.”
BackgroundSelf-citationQin, B., Jiao, X., Zhou, X.-C., Shi, B., Wang, J., Liu, K., Wu, Y., Ling, Y., & Zang, Y. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1929727 · Cited by 50 · see citing works
The role of opioids in cancer response to immunotherapy
Botticelli, A., Cirillo, A., Pomati, G., Cerbelli, B., Scagnoli, S., Roberto, M., Gelibter, A. J., Mammone, G., Calandrella, M. L., Cerbelli, E., et al. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-02784-8 · Cited by 45 · see citing works
Self-citationThrombotic Complications Associated with Immune Checkpoint Inhibitors
Wang, T., Khorana, A. A., & Carrier, M. (2021) · Cancers · doi:10.3390/cancers13184606 · Cited by 46 · see citing works
“This finding is interesting and hypothesis-generating for future investigation [49].”
BackgroundKim, C. G., Koh, J.-Y., Shin, S.-J., Shin, J.-H., Hong, M., Chung, H. C., Rha, S. Y., Kim, H. S., Lee, C.-K., Lee, J. H., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101251 · Cited by 45 · see citing works
“24,25 In addition, preclinical and clinical studies have reported that imbalances in the microflora induced by ATB administration may negatively impact the outcomes of PFS, progression-free survival; OS, overall survival; PD-1, programmed cell death protein-1; HR, hazard ratio; CI, confidence…”
BackgroundPatel, J. S., Woo, Y., Draper, A., Jansen, C. S., Carlisle, J. W., Innominato, P. F., Lévi, F., Dhabaan, L., Master, V. A., Bilen, M. A., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-008011 · Cited by 47 · see citing works
Peng, K., Chen, K., Teply, B. A., Yee, G. C., Farazi, P. A., & Lyden, E. R. (2021) · Annals of Pharmacotherapy · doi:10.1177/10600280211033938 · Cited by 41 · see citing works
Wang, Y., Yang, M., Tao, M., Liu, P., Kong, C., Li, H., Chen, Y., Yin, X., & Yan, X. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108031 · Cited by 40 · see citing works
Chen, B., Chen, Y., Dragomir, M. P., Chi, D., Chen, W., Horst, D. A., Călin, G. A., & Li, Q. (2022) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359221111703 · Cited by 38 · see citing works
Chiang, C., Chiang, C., Peng, C.-Y., Hsia, Y. P., See, X. Y., Horng, C., Chang, Y.-C., Shen, X.-E., Wang, S., Tsai, T.-C., et al. (2022) · European Journal of Cancer · doi:10.1016/j.ejca.2022.07.006 · Cited by 38 · see citing works
Lai, H., Liu, Y., Wu, J., Cai, J., Hui, J., Xu, Y., & Deng, S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1078766 · Cited by 37 · see citing works
“6% others) treated with PD-1/PD-L1 inhibitors (Cortellini et al., 2020), and a meta-analysis reported that concurrent use of lowdose aspirin was associated with better progression-free survival in cancer patients receiving immune checkpoint inhibitors, including NSCLC (Zhang et al.”
BackgroundPredictive biomarkers of response to immune checkpoint inhibitors in hepatocellular carcinoma
Muhammed, A., D’Alessio, A., Enica, A., TALBOT, T. L., Fulgenzi, C. A. M., Nteliopoulos, G., Goldin, R. D., Cortellini, A., & Pinato, D. J. (2022) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2022.2049244 · Cited by 35 · see citing works
“report rapid changes in the composition of gut microbiota consequent to short-term shifts between purely animal or plant-based diets [103], while multiple studies corroborate an impaired response to therapy in conjunction with antibiotics, pointing to the disruption of eubiosis as a possible explanation [104,105].”
BackgroundSelf-citationButi, S., Bersanelli, M., Perrone, F., Sergio Bracarda, A., Maïo, M. D., Giusti, R., Nigro, O., Cortinovis, D. L., Aerts, J. G. J. V., Guaitoli, G., et al. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.03.041 · Cited by 35 · see citing works
Self-citationProton Pump Inhibitors and Cancer: Current State of Play
Bridoux, M., Simon, N., & Turpin, A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.798272 · Cited by 35 · see citing works
Dimitriou, F., Staeger, R., Ak, M., Maissen, M., Kudura, K., Barysch, M. J., Levesque, M. P., Cheng, P. F., Dummer, R., & Mangana, J. (2021) · Cancers · doi:10.3390/cancers13122931 · Cited by 34 · see citing works
“In another recent multicenter observational study on concomitant medications and outcomes in patients with solid tumors treated with ICIs, patients with steroids at baseline for cancer-related indications had significantly worse PFS and OS than those without or those with steroids for non-cancer-related indications [3…”
BackgroundPaderi, A., Gambale, E., Botteri, C., Giorgione, R., Lavacchi, D., Brugia, M., Mazzoni, F., Giommoni, E., Bormioli, S., Amedei, A., et al. (2021) · Molecules · doi:10.3390/molecules26195789 · Cited by 34 · see citing works
“However, even if the detrimental effect observed in clinical outcomes from ICIs could have biological plausibility in light of the steroid immunosuppressive activity, the strength and reliability of the relationship have only been extrapolated from retrospective/post hoc analyses [12].”
BackgroundPietrzak, B., Tomela, K., Olejnik-Schmidt, A., Galus, Ł., Mackiewicz, J., Kaczmarek, M., Mackiewicz, A., & Schmidt, M. (2022) · Cancers · doi:10.3390/cancers14215369 · Cited by 36 · see citing works
Kawachi, H., Yamada, T., Tamiya, M., Negi, Y., Gotô, Y., Nakao, A., Shiotsu, S., Tanimura, K., Takeda, T., Okada, A., et al. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.22915 · Cited by 32 · see citing works
Immune checkpoint inhibitors and acute kidney injury
Zhou, P., Gao, Y., Kong, Z., Wang, J., Si, S., Han, W., Li, J., Lv, Z., & Wang, R. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1353339 · Cited by 33 · see citing works
Angiotensin receptor blocker attacks armored and cold tumors and boosts immune checkpoint blockade
Mei, J., Chu, J., Yang, K. G., Luo, Z., Yang, J., Xu, J., Li, Q., Zhang, Y., Zhang, Q., Wan, M., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009327 · Cited by 32 · see citing works
“14 In our previous report, we revealed the significance of cholesterol synthesis in non-small cell lung cancer (NSCLC) and demonstrated the improved therapeutic efficacy of ICB in combination with statins.”
Chang, Y., Lin, W.-Y., Chang, Y.-C., Huang, C.-H., Tzeng, H.-E., Abdul-Lattif, E., Wang, T.-H., Tseng, T.-H., Kang, Y., & Chi, K. (2022) · Cancers · doi:10.3390/cancers15010284 · Cited by 31 · see citing works
“Concomitant use of various medications has also been investigated to determine whether they alter the effectiveness of ICIs [9,10].”
BackgroundMellgard, G. S., Patel, V. G., Zhong, X., Joshi, H. N., Qin, Q., Wang, B., Parikh, A. B., Jun, T. W., Alerasool, P., Garcia, P., et al. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-04159-y · Cited by 30 · see citing works
“In this clinical context, two retrospective datasets for melanoma and NSCLC have each confirmed that the addition of BB was associated with improved OS (Kokolus et al. 2018; Cortellini et al. 2020; Wang et al. 2020; Gandhi et al. 2021; Oh et al. 2021).”
BackgroundLiu, C., Guo, H., Mao, H., Tong, J., Yang, M., & Yan, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.753234 · Cited by 29 · see citing works
“(20) 2020 69 Europe Multiple PD-(L)1 NA 491 1012 Within”
Yan, X., Liu, P., Li, D., Hu, R. Y., Tao, M., Zhu, S., Wu, W., Yang, M., & Qu, X. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109383 · Cited by 29 · see citing works
Gut–lung axis: role of the gut microbiota in non-small cell lung cancer immunotherapy
Zhang, H., & Xu, Z. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1257515 · Cited by 30 · see citing works
Yang, Y. A., Qi, J., Hu, J., Zhou, Y., Zheng, J., Deng, W., Inam, M., Guo, J., Xie, Y., Li, Y., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216765 · Cited by 28 · see citing works
Preclinical models of cardiotoxicity from immune checkpoint inhibitor therapy
Buehning, F., Lerchner, T., Vogel, J., Hendgen-Cotta, U. B., Totzeck, M., Rassaf, T., & Michel, L. (2024) · Basic Research in Cardiology · doi:10.1007/s00395-024-01070-0 · Cited by 27 · see citing works
Takada, K., Buti, S., Bersanelli, M., Shimokawa, M., Takamori, S., Matsubara, T., Takenaka, T., Okamoto, T., Hamatake, M., Tsuchiya‐Kawano, Y., et al. (2022) · European Journal of Cancer · doi:10.1016/j.ejca.2022.06.002 · Cited by 27 · see citing works
Self-citationInsulin resistance and cancer: molecular links and clinical perspectives
Caturano, A., Erul, E., Nilo, R., Nilo, D., Russo, V., Rinaldi, L., Acierno, C., Gemelli, M., Ricotta, R., Sasso, F. C., et al. (2025) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-025-05245-8 · Cited by 26 · see citing works
“However, conflicting evidence highlights the need for further prospective studies to clarify its role [196].”
Russano, M., Cortellini, A., Giusti, R., Russo, A., Zoratto, F., Rastelli, F., Gelibter, A. J., Chiari, R., Nigro, O., Tursi, M. D., et al. (2021) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-021-03045-9 · Cited by 26 · see citing works
Self-citationMao, Z., Jia, X., Jiang, P., Wang, Q., Zhang, Y., Li, Y.-L., Fu, X., Jiao, M., Jiang, L., Liu, Z., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.861723 · Cited by 26 · see citing works
“The remaining studies (26, 28, 29, 32, 35) included both NSCLC and melanoma or other types of cancer.”
BackgroundInfluentialMorphine treatment restricts response to immunotherapy in oral squamous cell carcinoma
McIlvried, L. A., Matos, A. A. M., Yuan, M. M., Atherton, M. A., Obuekwe, F., Nilsen, M. L., Nikpoor, A. R., Talbot, S., Bruno, T. C., Taggart, D. N., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009962 · Cited by 25 · see citing works
“46 To extend these findings, our in silico bioinformatic analysis found that HNSCC tumor-infiltrating OPRM1 - expressing CD8 + T cells exhibited differential transcriptomic phenotype compared with OPRM1 - negative cells suggesting dysfunc-tionality, decreased cytokine expression and increased…”
van Dorst, D. C. H., van Doorn, L., Colafella, K. M. M., Manintveld, O. C., Hassing, H. C., Danser, A. H. J., Mathijssen, R. H. J., & Versmissen, J. (2021) · Clinical Science · doi:10.1042/cs20200300 · Cited by 25 · see citing works
Mechanisms of Resistance to Immunotherapy in Hepatocellular Carcinoma
Manfredi, G. F., Celsa, C., John, C., Jones, C., Acuti, N., Scheiner, B., Fulgenzi, C. A. M., Korolewicz, J., Pinter, M., Gennari, A., et al. (2023) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s291553 · Cited by 26 · see citing works
“Concomitant use of these three drug types has been associated with poor patient outcomes in retrospective analyses, 168,169 with some evidence that they have a cumulative effect on predicting OS and PFS in patients with advanced cancer receiving ICI therapy.”
BackgroundSelf-citationParisi, C., Abdayem, P., Tagliamento, M., Besse, B., Planchard, D., Remón, J., Minuti, G., Cappuzzo, F., & Barlési, F. (2024) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2024.102845 · Cited by 26 · see citing works
Statin use improves the efficacy of nivolumab in patients with advanced renal cell carcinoma
Santoni, M., Massari, F., Matrana, M. R., Basso, U., Giorgi, U. D., Aurilio, G., Buti, S., Incorvaia, L., Rizzo, M., Martignetti, A., et al. (2022) · European Journal of Cancer · doi:10.1016/j.ejca.2022.04.035 · Cited by 23 · see citing works
Chiang, C., Chen, Y., Chiang, C., Chen, C.-Y., Chang, Y.-C., Wang, S., See, X. Y., Horng, C., Peng, C.-Y., Hsia, Y. P., et al. (2023) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-022-03363-6 · Cited by 24 · see citing works
Shen, J., Hou, H. Y., Liang, B., Guo, X., Chen, L., Yang, Y., & Wang, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1155104 · Cited by 24 · see citing works
“Cortellini et al 2020 (37) Article RP Europe 313/1012 (30.”
BackgroundRodríguez‐Berriguete, G., Puliyadi, R., Machado, N., Barberis, A., Prevo, R., McLaughlin, M., Buffa, F. M., Harrington, K. J., & Higgins, G. S. (2024) · Cell Death and Disease · doi:10.1038/s41419-023-06405-8 · Cited by 24 · see citing works
Acute Kidney Injury Induced by Immune Checkpoint Inhibitors
Tian, R., Liang, J., Li, R., & Zhou, X. (2022) · Kidney Diseases · doi:10.1159/000520798 · Cited by 22 · see citing works
Cani, M., Bironzo, P., Garetto, F., Buffoni, L., & Cotogni, P. (2022) · Healthcare · doi:10.3390/healthcare11010116 · Cited by 22 · see citing works
“tumour burden and may therefore represent another confounding factor [3].”
BackgroundInternò, V., Sergi, M. C., Metta, M. E., Guida, M., Trerotoli, P., Strippoli, S., Circelli, S., Porta, C., & Tucci, M. (2023) · Cancers · doi:10.3390/cancers15051542 · Cited by 22 · see citing works
Self-citationCao, T., Zhou, X., Wu, X., & Zou, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1207544 · Cited by 23 · see citing works
Liao, Y., Lin, Y., Ye, X., & Shen, J. (2025) · JCO Oncology Practice · doi:10.1200/op-24-00583 · Cited by 22 · see citing works
Impact of the ONCOBIOME network in cancer microbiome research
Zitvogel, L., Derosa, L., Routy, B., Loibl, S., Heinzerling, L., de Vries, I. J. M., Engstrand, L., ONCOBIOME Network, Silva, C. A. C., Barbieri, D., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03608-8 · Cited by 23 · see citing works
“…between broad-spectrum antibiotic use and prognosis was, at least initially, independent of possible confounding factors including age, performance status and comorbidities 3,4 and was observed in patients receiving immunotherapy-based regimens but not in those receiving chemotherapy alone 91,92 .”
Zhao, S., Lu, Z., Zhao, F., Tang, S., Zhang, L., & Feng, C. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1538969 · Cited by 21 · see citing works
“Immune checkpoint inhibitors (ICIs) dramatically altered the landscape of cancer treatment, and markedly improved the prognosis (1 – 3), particularly for patients with melanoma and non-small cell lung cancer (NSCLC) (4 – 6).”
InfluentialJu, M., Gao, Z., Liu, X., Zhou, H., Wang, R., Zheng, C., Dong, D., Zhu, Z., & Li, K. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-04513-0 · Cited by 21 · see citing works
Bar-Hai, N., Ben‐Betzalel, G., Stoff, R., Grynberg, S., Schachter, J., Shapira‐Frommer, R., & Asher, N. (2023) · Cancers · doi:10.3390/cancers15113041 · Cited by 20 · see citing works
“medication concordantly related to a poorer response rate, PFS and OS in 1012 patients [39].”
BackgroundVos, W. G., Lutgens, E., & Seijkens, T. T. P. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005611 · Cited by 20 · see citing works
Concomitant Medication Effects on Immune Checkpoint Inhibitor Efficacy and Toxicity
Sieber, B., Strauss, J., Li, Z., & Gatti-Mays, M. E. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.836934 · Cited by 19 · see citing works
“(37) evaluated the effect of ACEi/ARBs in patients with solid tumors, while Failing et al.”
BackgroundResultInfluentialRassy, E., Dalban, C., Colomba, É., Derosa, L., Silva, C. A. C., Négrier, S., Chevreau, C., Gravis, G., Oudard, S. M., Laguerre, B., et al. (2022) · Clinical Genitourinary Cancer · doi:10.1016/j.clgc.2022.07.003 · Cited by 19 · see citing works
Yu, X., Wu, R., Ji, Y., Huang, M., & Feng, Z. (2022) · Diagnostics · doi:10.3390/diagnostics12123157 · Cited by 19 · see citing works
“However, systemic prophylactic antibiotic use greatly reduces the progression-free survival and overall survival of patients treated with ICPis, possibly by mechanisms related to antibiotic-induced alterations in the intestinal flora and effects on the body’s immunity [23].”
BackgroundPizzutilo, E. G., Romanò, R., Roazzi, L., Agostara, A. G., Oresti, S., Zeppellini, A., Giannetta, L. G., Cerea, G., Signorelli, D., Siena, S., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-23-0161 · Cited by 19 · see citing works
Yuan, M., Han, S., Jia, Y., Feng, J., Liu, D., Su, Z., & Liu, X. (2022) · International Journal of Clinical Practice · doi:10.1155/2022/4938539 · Cited by 18 · see citing works
Wu, L. Y., Hyfte, G. V., Özbek, U., Reincke, M., Gampa, A., Mohamed, Y. I., Nishida, N., Wietharn, B., Amara, S., Lee, P., et al. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1128569 · Cited by 18 · see citing works
Self-citationHatanaka, T., Kakizaki, S., Hiraoka, A., Tada, T., Hirooka, M., Kariyama, K., Tani, J., Atsukawa, M., Takaguchi, K., Itobayashi, E., et al. (2023) · Hepatology Research · doi:10.1111/hepr.13905 · Cited by 18 · see citing works
“A study evaluated 1512 patients with NSCLC based on the pooled data from phase II and phase III studies, revealing that patients treated with PPIs and antibiotics showed significantly shorter PFS and OS in patients receiving atezolizumab monotherapy.16 Another study investigated the association between the concomitant…”
BackgroundInfluentialCoschi, C. H., & Juergens, R. A. (2023) · Current Oncology · doi:10.3390/curroncol31010001 · Cited by 20 · see citing works
“The mechanisms by which they are thought to do so are via direct or indirect effects on the host immune system [69,72,73].”
BackgroundStatin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma
Wang, J., Liu, C., Hu, R., Wu, L., & Li, C. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1324140 · Cited by 19 · see citing works
Santini, D., Zeppola, T., Russano, M., Citarella, F., Anesi, C., Buti, S., Tucci, M., Russo, A., Sergi, M. C., Adamo, V., et al. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-02937-9 · Cited by 18 · see citing works
Self-citationBouferraa, Y., Chedid, A., Amhaz, G., Lakkiss, A. E., Mukherji, D., Temraz, S. N., & Shamseddine, A. I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158036 · Cited by 18 · see citing works
“In a multicenter observational study involving 1012 treated with CPIS, PPIs were shown to be associated with a significantly higher risk of disease progression and death [88].”
BackgroundA Forgotten Corner in Cancer Immunotherapy: The Role of Lipids
Yu, Y., Gao, L., Wang, Y., Xu, B., Maswikiti, E. P., Li, H., Peng, Z., Tao, P., Xiang, L., Gu, B., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.751086 · Cited by 18 · see citing works
Kött, J., Zell, T., Zimmermann, N., Rünger, A., Smit, D. J., Abeck, F., Geidel, G., Hansen, I., Heidrich, I., Weichenthal, M., et al. (2024) · European Journal of Cancer · doi:10.1016/j.ejca.2024.115159 · Cited by 17 · see citing works
Statins and renal cell carcinoma: Antitumor activity and influence on cancer risk and survival
Santoni, M., Monteiro, F. S. M., Massari, F., Abahssain, H., Aurilio, G., Molina‐Cerrillo, J., Myint, Z. W., Ortego, I., Battelli, N., & Grande, E. (2022) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2022.103731 · Cited by 17 · see citing works
Deng, R., Zhang, H., Li, Y., & Shi, Y. (2022) · Journal of Immunotherapy · doi:10.1097/cji.0000000000000442 · Cited by 17 · see citing works
Association of Pulmonary Sepsis and Immune Checkpoint Inhibitors: A Pharmacovigilance Study
Xia, S., Gong, H., Zhao, Y., Guo, L., Wang, Y., Zhang, B., Sarangdhar, M., Noguchi, Y., & Yan, M. (2022) · Cancers · doi:10.3390/cancers15010240 · Cited by 17 · see citing works
“Previous studies [18,19] showed that concomitant medications, such as steroids, proton pump inhibitors (PPI), and antibiotics, might affect clinical outcomes with immune checkpoint inhibitors.”
BackgroundColard‐Thomas, J., Thomas, Q. D., & Viala, M. (2023) · Cancers · doi:10.3390/cancers15082276 · Cited by 17 · see citing works
“03) in a 1012-patient retrospective study [114].”
ResultMevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA
Zhang, W., Pan, X., Xu, Y., Guo, H., Zheng, M., Chen, X., Wu, H., Luan, F., He, Q., Ding, L., et al. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.04.002 · Cited by 16 · see citing works
Scarpa, J. R., Montagna, G., Plitas, G., Gulati, A., Fischer, G. W., & Mincer, J. S. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1267532 · Cited by 17 · see citing works
Statin Use With Immune Checkpoint Inhibitors and Survival in Nonsmall Cell Lung Cancer
Marrone, M. T., Reuss, J. E., Crawford, A., Neelon, B., Liu, J. O., Brahmer, J. R., & Platz, E. A. (2024) · Clinical Lung Cancer · doi:10.1016/j.cllc.2024.12.008 · Cited by 17 · see citing works
Cesano, A., Augustin, R. C., Barrea, L., Bedognetti, D., Bruno, T. C., Carturan, A., Hammer, C., Ho, W. S., Kather, J. N., Kirchhoff, T., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-008876 · Cited by 18 · see citing works
Recent advances in primary resistance mechanisms against immune checkpoint inhibitors
Li, Y.-Z., & Zhang, H.-M. (2021) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000802 · Cited by 17 · see citing works
Rebuzzi, S. E., Banna, G. L., Murianni, V., Damassi, A., Giunta, E. F., Fraggetta, F., Giorgi, U. D., Cathomas, R. L., Rescigno, P., Brunelli, M., et al. (2021) · Cancers · doi:10.3390/cancers13215517 · Cited by 17 · see citing works
Leveraging beneficial microbiome-immune interactions via probiotic use in cancer immunotherapy
Jani, C., Edwards, K., Bhanushali, C. D., Zheng, X. X., Salazar, A. S., Lopes, G. D. L., Jr., & Watson, D. C. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1713382 · Cited by 17 · see citing works
Cardiovascular Effects of Immune Checkpoint Inhibitors: More Than Just Myocarditis
Inno, A., Tarantini, L., Parrini, I., Spallarossa, P., Maurea, N., Bisceglia, I., Silvestris, N., Russo, A. D., & Gori, S. (2023) · Current Oncology Reports · doi:10.1007/s11912-023-01411-7 · Cited by 16 · see citing works
Self-citationChorti, E., Kowall, B., Hassel, J. C., Schilling, B., Sachse, M., Gutzmer, R., Loquai, C., Kähler, K. C., Hüsing, A., Gilde, C., et al. (2024) · European Journal of Cancer · doi:10.1016/j.ejca.2024.113536 · Cited by 16 · see citing works
- Authors
- Cortellini, A., Tucci, M., Adamo, V., Stucci, L. S., Russo, A., Tanda, E. T., Spagnolo, F., Rastelli, F., Bisonni, R., Santini, D., Russano, M., Anesi, C., Giusti, R., Filetti, M., Marchetti, P., Botticelli, A., Gelibter, A., Occhipinti, M. A., Marconcini, R., Vitale, M. G., Nicolardi, L., Chiari, R., Bareggi, C., Nigro, O., Tuzi, A., De Tursi, M., Petragnani, N., Pala, L., Bracarda, S., Macrini, S., Inno, A., Zoratto, F., Veltri, E., Di Cocco, B., Mallardo, D., Vitale, M. G., Pinato, D. J., Porzio, G., Ficorella, C., & Ascierto, P. A.
- Affiliations
- University of L'Aquila (IT)
- Istituto Tumori Bari (IT)
- University of Messina (IT)
- University of Bari Aldo Moro (IT)
- Ospedale Policlinico San Martino (IT)
- Medical Oncology, ASUR District Area 4 Fermo, Fermo, Italy
- Università Campus Bio-Medico (IT)
- Azienda Ospedaliera Sant'Andrea (IT)
- Policlinico Umberto I (IT)
- Sapienza University of Rome (IT)
- Azienda Ospedaliera Universitaria Pisana (IT)
- Azienda Ospedaliero-Universitaria di Modena (IT)
- UOC Oncologia Padova Sud, Azienda ULSS 6 Euganea, Padova, Italy
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Ospedale di Circolo e Fondazione Macchi (IT)
- Department of Medical, Oral and Biotechnological Sciences, Gabriele d'Annunzio University of Chieti and Pescara, Chieti, Italy
- University of Chieti-Pescara (IT)
- European Institute of Oncology (IT)
- Medical Oncology, Azienda Ospedaliera S. Maria, Terni, Italy
- Azienda Ospedaliera S.Maria (IT)
- Ospedale Sacro Cuore Don Calabria (IT)
- Ospedale Santa Maria Goretti (IT)
- Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- Hammersmith Hospital (GB)
- Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy
- Corresponding author
- Cortellini, Alessio
- ORCID
- Cortellini, Alessio
- Tucci, Marco
- Adamo, Vincenzo
- Stucci, Luigia Stefania
- Russo, Alessandro
- Tanda, Enrica Teresa
- Spagnolo, Francesco
- Bisonni, Renato
- Santini, Daniele
- Russano, Marco
- Giusti, Raffaele
- Filetti, Marco
- Marchetti, Paolo
- Botticelli, Andrea
- Gelibter, Alain
- Occhipinti, Mario Alberto
- Marconcini, Riccardo
- Vitale, Maria Giuseppa
- Nicolardi, Linda
- Chiari, Rita
- Nigro, Olga
- Petragnani, Nicola
- Pala, Laura
- Macrini, Serena
- Inno, Alessandro
- Zoratto, Federica
- Veltri, Enzo
- Mallardo, Domenico
- Vitale, Maria Grazia
- Pinato, David James
- Porzio, Giampiero
- Ficorella, Corrado
- Ascierto, Paolo Antonio
- Venue
- Journal for ImmunoTherapy of Cancer
- Publisher
- BMJ
- Published
- 2020-11
- Volume
- 8
- Issue
- 2
- Pages
- e001361
- ISSN
- 2051-1426 (ISSN-L)
- PMC
- PMC7646355
- OpenAlex
- W3097304584
- Cited by
- 275
- References
- 58
- Citations by year
- 2026: 36 · 2025: 46 · 2024: 50 · 2023: 56 · 2022: 50 · 2021: 36 · 2020: 1
- FWCI
- 12.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion, other-oa)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, cc-by-nc)
- Funders
- Institute for Translational Medicine and Therapeutics
- Wellcome Trust (PS3416)
- Cancer Research UK
- National Institute for Health and Care Research
- Imperial Experimental Cancer Medicine Centre
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Oncology › COVID-19 and healthcare impacts
- Keywords
- PD-1/PD-L1 inhibitors, immune checkpoint inhibitors, concomitant medications, drug-drug interactions, corticosteroids, proton pump inhibitors, statins, aspirin, beta-blockers, antibiotics, objective response rate, progression-free survival, overall survival, non-small cell lung cancer, melanoma, renal cell carcinoma, stage IV cancer, immunotherapy safety
- MeSH terms
- Immune Checkpoint Inhibitors, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Retrospective Studies, Young Adult
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