Vol 15, No 3 (2021)
Review paper
Published online: 2021-07-05
The impact of antibiotics and glucocorticoids on the results of immunomodulatory antibody treatment in cancer patients
12
, 3
, 3
DOI: 10.5603/PMPI.2021.0015
Palliat Med Pract 2021;15(3):233-240.
Abstract
Cancer cells avoid elimination through the mechanism of immunosuppression, which consists in modulating
antigens and affecting the activation of the complement system. In 2011, authorities registered
a monoclonal antibody and the first medication from the group of immunological checkpoints, ipilimumab,
which activates T lymphocytes through unblocking the possibility of presenting antigens to cells after
binding with cytotoxic T cell antigen (CTLA-4 ). Other targets of the drugs from this group were described:
programmed death cell receptor 1 (PD-1), located on T lymphocytes, and programmed death cell ligand 1
(PD-L1), located on cancer cells. Immunotherapy significantly improved the prognosis of patients diagnosed
with melanoma, renal cell carcinoma, squamous cell carcinomas of the head and neck, non-small
cell lung cancer and other cancers
Glucocorticoids are often used in the treatment of symptoms in cancer patients. They are also administered
during immunotherapy in the case of immune-related adverse events. Antibiotics also constitute a group of
medications that are widely used in cancer patients. Since both glucocorticoids and antibiotics can decrease
the effectiveness of immunotherapy, physicians should carefully consider the expected benefits and the possible
negative impact of their administration on the survival time of cancer patients before prescribing them.
Keywords: cancer immunotherapyantibioticsglucocorticoidsside effects
References
- Motzer RJ, Escudier B, George S, et al. CheckMate 025 investigators, CheckMate 025 investigators, CheckMate 025 Investigators. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015; 373(19): 1803–1813.
- Weber J, D'Angelo S, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. The Lancet Oncology. 2015; 16(4): 375–384.
- Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017; 18(3): 312–322.
- Levy S, Aarts MJB, Eskens FA, et al. Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort. J Immunother Cancer. 2020; 8(2).
- Ferris RL, Blumenschein G, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016; 375(19): 1856–1867.
- Gandara DR, Kowanetz M, Mok T, et al. Blood-based biomarkers for cancer immunotherapy: Tumor mutational burden in blood (bTMB) is associated with improved atezolizumab (atezo) efficacy in 2L+ NSCLC (POPLAR and OAK). Annals of Oncology. 2017; 28: v460.
- Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2019; 381(16): 1535–1546.
- Burtness B, Harrington KJ, Greil R, et al. KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019; 394(10212): 1915–1928.
- Migden MR, Rischin D, Schmults CD, et al. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med. 2018; 379(4): 341–351.
- Antonia SJ, Villegas A, Daniel D, et al. PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 377(20): 1919–1929.
- Mansfield AS, Każarnowicz A, Karaseva N, et al. IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018; 379(23): 2220–2229.
- Powles T, van der Heijden MS, Castellano D, et al. DANUBE study investigators. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020; 383(13): 1218–1230.
- Magee DE, Hird AE, Klaassen Z, et al. Adverse event profile for immunotherapy agents compared with chemotherapy in solid organ tumors: a systematic review and meta-analysis of randomized clinical trials. Ann Oncol. 2020; 31(1): 50–60.
- https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf. (07.12.2020).
- Kartolo A, Sattar J, Sahai V, et al. Predictors of immunotherapy-induced immune-related adverse events. Curr Oncol. 2018; 25(5): e403–e410.
- Khan OF, Monzon J. Diagnosis, monitoring, and management of adverse events from immune checkpoint inhibitor therapy. Curr Oncol. 2020; 27(Suppl 2): S43–S50.
- Denton A, Shaw J. Corticosteroid prescribing in palliative care settings: a retrospective analysis in New Zealand. BMC Palliat Care. 2014; 13(1): 7.
- Rolston KVI. Infections in Cancer Patients with Solid Tumors: A Review. Infect Dis Ther. 2017; 6(1): 69–83.
- Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002; 3(11): 991–998.
- Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646–674.
- https://www.nobelprize.org/prizes/medicine/2018/press-release/. (07.12.2020).
- Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996; 271(5256): 1734–1736.
- Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992; 11(11): 3887–3895.
- Dong H, Zhu G, Tamada K, et al. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999; 5(12): 1365–1369.
- Oiseth S, Aziz M. Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead. Journal of Cancer Metastasis and Treatment. 2017; 3(10): 250.
- Derosa L, Hellmann MD, Spaziano M, et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol. 2018; 29(6): 1437–1444.
- Matson V, Fessler J, Bao R, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018; 359(6371): 104–108.
- Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018; 359(6371): 97–103.
- Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015; 350(6264): 1084–1089.
- Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018; 359(6371): 91–97.
- Pinato DJ, Howlett S, Ottaviani D, et al. Association of Prior Antibiotic Treatment With Survival and Response to Immune Checkpoint Inhibitor Therapy in Patients With Cancer. JAMA Oncol. 2019; 5(12): 1774–1778.
- Galli G, Triulzi T, Proto C, et al. Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer. Lung Cancer. 2019; 132: 72–78.
- Wilson BE, Routy B, Nagrial A, et al. The effect of antibiotics on clinical outcomes in immune-checkpoint blockade: a systematic review and meta-analysis of observational studies. Cancer Immunol Immunother. 2020; 69(3): 343–354.
- Elkrief A, Derosa L, Kroemer G, et al. The negative impact of antibiotics on outcomes in cancer patients treated with immunotherapy: a new independent prognostic factor? Ann Oncol. 2019; 30(10): 1572–1579.
- Yang M, Wang Y, Yuan M, et al. Antibiotic administration shortly before or after immunotherapy initiation is correlated with poor prognosis in solid cancer patients: An up-to-date systematic review and meta-analysis. Int Immunopharmacol. 2020; 88: 106876.
- Derosa L, Zitvogel L. Antibiotics impair immunotherapy for urothelial cancer. Nat Rev Urol. 2020; 17(11): 605–606.
- Tinsley N, Zhou C, Tan G, et al. Cumulative Antibiotic Use Significantly Decreases Efficacy of Checkpoint Inhibitors in Patients with Advanced Cancer. Oncologist. 2020; 25(1): 55–63.
- Ahmed J, Kumar A, Parikh K, et al. Use of broad-spectrum antibiotics impacts outcome in patients treated with immune checkpoint inhibitors. Oncoimmunology. 2018; 7(11): e1507670.
- Elkrief A, El Raichani L, Richard C, et al. Antibiotics are associated with decreased progression-free survival of advanced melanoma patients treated with immune checkpoint inhibitors. Oncoimmunology. 2019; 8(4): e1568812.
- Arbour KC, Mezquita L, Long N, et al. Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer. J Clin Oncol. 2018; 36(28): 2872–2878.
- De Giglio A, Mezquita L, Auclin E, et al. Impact of early introduction of steroid on immune-checkpoint inhibitors (ICI) in patients with advanced non-small cell lung cancer treated. Annals of Oncology. 2019; 30: xi16.
- Drakaki A, Luhn P, Wakelee H, et al. Association of systemic corticosteroids with overall survival in patients receiving cancer immunotherapy for advanced melanoma, non-small cell lung cancer or urothelial cancer in routine clinical practice. Annals of Oncology. 2019; 30: xi16–xi17.
- Koo MM, Hamilton W, Walter FM, et al. Symptom Signatures and Diagnostic Timeliness in Cancer Patients: A Review of Current Evidence. Neoplasia. 2018; 20(2): 165–174.
- Dumenil C, Massiani MA, Dumoulin J, et al. Clinical factors associated with early progression and grade 3-4 toxicity in patients with advanced non-small-cell lung cancers treated with nivolumab. PLoS One. 2018; 13(4): e0195945.
- Scott SC, Pennell NA. Early Use of Systemic Corticosteroids in Patients with Advanced NSCLC Treated with Nivolumab. J Thorac Oncol. 2018; 13(11): 1771–1775.
- Horvat TZ, Adel NG, Dang TO, 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 Clin Oncol. 2015; 33(28): 3193–3198.
- 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. Cancers (Basel). 2020; 12(3).
- Pan EY, Merl MY, Lin K. The impact of corticosteroid use during anti-PD1 treatment. J Oncol Pharm Pract. 2020; 26(4): 814–822.
- 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. Eur J Cancer. 2021; 145: 245–254.
- Janowitz T, Kleeman S, Vonderheide RH. Reconsidering Dexamethasone for Antiemesis when Combining Chemotherapy and Immunotherapy. Oncologist. 2021; 26(4): 269–273.
- Sheehan K, Price C, Hafez N. Optimizing Care for Patients With Adverse Events From Immunotherapeutics. Cancer J. 2020; 26(6): 537–542.
- Pauken KE, Dougan M, Rose NR, et al. Adverse Events Following Cancer Immunotherapy: Obstacles and Opportunities. Trends Immunol. 2019; 40(6): 511–523.
- Caspi RR. Immunotherapy of autoimmunity and cancer: the penalty for success. Nat Rev Immunol. 2008; 8(12): 970–976.
- Sznol M, Postow MA, Davies MJ, et al. Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management. Cancer Treat Rev. 2017; 58: 70–76.
- Byun DJ, Wolchok JD, Rosenberg LM, et al. Cancer immunotherapy - immune checkpoint blockade and associated endocrinopathies. Nat Rev Endocrinol. 2017; 13(4): 195–207.
- Weber JS, Hodi FS, Wolchok JD, et al. Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma. J Clin Oncol. 2017; 35(7): 785–792.
- https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy. (07.12.2020).
- Haanen JB, Carbonnel F, Robert C, et al. ESMO Guidelines Committee. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017; 28(suppl_4): iv119–iv142.
- Weber JS. Challenging Cases: Management of Immune-Related Toxicity. Am Soc Clin Oncol Educ Book. 2018; 38: 179–183.
- Londoño MC, Reig M. RETOINMUNO Multidisciplinary Group. Multidisciplinary Clinical Approach to Cancer Patients with Immune-Related Adverse Events Induced by Checkpoint Inhibitors. Cancers (Basel). 2020; 12(11).
- Xu C, Chen YP, Du XJ, et al. Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis. BMJ. 2018; 363: k4226.
- https://www.nccn.org/professionals/physician_gls/pdf/infections. (07.12.2020).
- Faje AT, Sullivan R, Lawrence D, et al. Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma. J Clin Endocrinol Metab. 2014; 99(11): 4078–4085.
- Rogado J, Sánchez-Torres JM, Romero-Laorden N, et al. Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients. Eur J Cancer. 2019; 109: 21–27.
- Chang CY, Park H, Malone DC, et al. Immune Checkpoint Inhibitors and Immune-Related Adverse Events in Patients With Advanced Melanoma: A Systematic Review and Network Meta-analysis. JAMA Netw Open. 2020; 3(3): e201611.
- Brahmer JR, Lacchetti C, Schneider BJ, et al. National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018; 36(17): 1714–1768.
- Shan C, Li X, Zhang J. Progress of immune checkpoint LAG-3 in immunotherapy. Oncol Lett. 2020; 20(5): 207.
- Du W, Yang M, Turner A, et al. TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action. Int J Mol Sci. 2017; 18(3).
- https://clinicaltrials.gov/ct2/show/NCT04225390 (15.02.2021).
- https://clinicaltrials.gov/ct2/show/NCT04640103 (15.02.2021).
