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Review on Immuno-Oncology Agents for Cancer Therapy


Affiliations
1 Ahinsa Institute of Pharmacy, Dondaicha 425408, India
     

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Until recently, cancer therapy comprised of four main types of treatment: surgery, radiotherapy, chemotherapy and targeted therapy. Over the past decade, immuno-oncology (IO) has emerged as a novel and important approach to cancer treatment through the stimulation of the body’s own immune system to kill cancer cells. This newly recognised method of treating cancer is rapidly developing, with many accelerated approvals by the US Food and Drug Administration and European Medicines Agency in 2019. Several therapeutic classes have emerged within IO, and are the focus of this review article. In particular, the immune checkpoint inhibitors have had remarkable success across multiple malignancies, and are the most well-established therapeutic class of IO agents to date. Biomarker testing for the programmed death-ligand 1 (PD-L1) checkpoint target has been developed and is now obligatory before treatment with pembrolizumab (Keytruda, Merck) when used for non- small-cell lung carcinoma, gastric cancer, head and neck squamous cell carcinoma and cervical cancer, as well as before treatment with atezolizumab (Tecentriq, Roche) when used for urothelial carcinoma. However, ambiguity remains as to the relevance of PD-L1 expression for checkpoint inhibition therapy for other tumour types. More recently, combining IO agents with conventional therapies has been evaluated with some significant improvements in patient outcomes. While IO agents are rapidly changing the standard of care for people with cancer, there are still many challenges to overcome in terms of managing their toxicities and ensuring that healthcare systems, such as the NHS, can afford the high cost of these therapies. The IO pipeline also includes chimeric antigen receptor T-cell therapies and cancer vaccines, both of which show great promise for the future but have their own unique toxicity and cost-effectiveness issues.


Keywords

Biomarkers, Cancer, Immune checkpoint inhibitors, Immune-oncology, Oncology
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  • Macmillan. BCG treatment for non-invasive bladder cancer. 2016. Available at: https://www.macmillan.org.uk/information-and- support/bladder-cancer/ non-invasive-bladder-cancer/treating/bcg- treatment/bcg-treatment-noninvasive-bladder.html#3977 (accessed May 2020) National Institute for Health and Care Excellence. Managing non-muscleinvasive bladder cancer. 2019. Available at: https://pathways.nice.org.uk/ pathways/bladder-cancer/managing- non-muscle-invasive-bladder-cancer (accessed May 2020).
  • Cancer Research Institute. Immunotherapy treatment types. 2019. Available at: https://www.cancerresearch.org/immunotherapy/treatment-types (accessed May 2020)
  • Geynisman DM Chien CR, Smieliauskas F et al. Economic evaluation of therapeutic cancer vaccines and immunotherapy: a systematic review. Hum Vaccin Immunother 2014;10(11):3415– 3424. doi: 10.4161/hv.29407
  • Zhang H and Chen J. Current status and future directions of cancer immunotherapy. J Cancer 2018;9(10):1773–1781. doi: 10.7150/jca.24577
  • Galluzzi L, Vacchelli E, Bravo-San Pedro JM et al. Classification of current anticancer immunotherapies. Oncotarget 2014 Dec;5(24):12472–12508. doi: 10.18632/oncotarget.2998
  • McKee S. EU approves first CAR-T therapies. 2018. Available at: http:// www.pharmatimes.com/news/eu_approves_first_car- t_therapies_1250347 (accessed May 2020)
  • Tang J, Shalabi A and Hubbard-Lucey VM. Comprehensive analysis of the clinical immuno-oncology landscape. Ann Oncol 2018;29(1):84–91. doi: 10.1093/annonc/mdx755
  • Cristescu R, Mogg R, Ayers M et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy. Science 2018. 362(6411):eaar3593. doi: 10.1126/science.aar3593
  • Teixidó C, Vilariño N, Reyes R and Reguart N. PD-L1 expression testing in non-small cell lung cancer. Ther Adv Med Oncol 2018;10:1758835918763493. doi: 10.1177/1758835918763493
  • Combining IO agents with conventional therapies has provided significant improvements in patient outcomes in some cases. • The two main challenges for IO agents are managing their toxicities and affording the high cost of these novel therapies. S24
  • The Pharmaceutical Journal Vol 304 No 7937 May 2020 May 2020 NO 7937 VOL 304 The Pharmaceutical Journal S25 Review Review chemotherapy. Transl Oncol 2016;9(1):64–69. doi: 10.1016/j.tranon.2016.01.003
  • Chen D, Irving B and Hodi FS. Molecular pathways: next- generation immunotherapy — inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 2012;18(24):6580– 6587. doi: 10.1158/1078-0432.CCR-12-1362
  • Topalian SL, Hodi FS, Brahmer JR et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366(26): 2443–2454. doi: 10.1056/NEJMoa1200690
  • Shen X and Zhao B. Efficacy of PD-1 or PD-L1 inhibitors and PD- L1 expression status in cancer: meta-analysis. BMJ 2018;362. doi: 10.1136/bmj.k3529
  • US National Library of Medicine. Study of BMS-936558 (nivolumab) compared to docetaxel in previously treated advanced or metastatic squamous cell non-small cell lung cancer (NSCLC; CheckMate 017). 2012. Available at: https://clinicaltrials.gov/ct2/show/NCT01642004 (accessed May 2020)
  • US National Library of Medicine. Study of nivolumab (BMS- 936558) vs. everolimus in pre-treated advanced or metastatic clear-cell renal cell carcinoma (CheckMate 025). 2012. Available at: https://clinicaltrials.gov/ct2/ show/results/NCT01668784 (accessed May 2020)
  • US National Library of Medicine. A study of atezolizumab compared with docetaxel in participants with locally advanced or metastatic non-small cell lung cancer who have failed platinum- containing therapy (OAK). 2013. Available at: https://clinicaltrials.gov/ct2/show/NCT02008227 (accessed May 2020)
  • Dempke WCM, Fenchel K, and Dale SP. Programmed cell death ligand-1 (PD-L1) as a biomarker for non- small cell lung cancer (NSCLC) treatment — are we barking up the wrong tree? Transl Lung Cancer Res 2018;7(Suppl 3):S275–S279. doi: 10.21037/tlcr.2018.04.18
  • 38. Robainas M, Otano R, Bueno S and Ait-Oudhia S. Understanding the role of PD-L1/PD1 pathway blockade and autophagy in cancer therapy. Onco Targets Ther 2017;10:1803– 1807. doi: 10.2147/OTT.S132508
  • Scheel AH, Dietel M, Heukamp LC et al. Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod Pathol 2016;29(10):1165–1172. doi: 10.1038/modpathol.2016.117
  • Nanda S. Avelumab plus axitinib ‘new first-line standard of care’ for advanced RCC. 2018. Available at: https://oncologypro.esmo.org/OncologyNews/Daily- News/Avelumab-Plus-Axitinib-New-First-Line-Standard-OfCare- For-Advanced-RCC (accessed May 2020)
  • Williams, L. Pembrolizumab achieves survival improvements across PDL1 status in KEYNOTE-407 trial. 2018. Available at: https://oncologypro. esmo.org/Oncology-News/Daily- News/Pembrolizumab-AchievesSurvival-Improvements-Across- PD-L1-Status-In-KEYNOTE-407-Trial (accessed May 2020)
  • McLaughlin J, Han G, Schalper KA et al. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol 2016;2(1):46–54. doi: 10.1001/jamaoncol.2015.3638
  • Arkenau HT. PD-L1 in cancer: ESMO biomarker factsheet. 2017. Available at: https://oncologypro.esmo.org/Education- Library/Factsheets-onBiomarkers/PD-L1-in-Cancer (accessed May 2020)
  • 44. Ribas A and Hu-Lieskovan S. What does PD-L1 positive or negative mean? J Exp Med 2016;213(13): 2835–2840. doi: 10.1084/jem.20161462
  • Bassanelli M, Sioletic S, Martini M et al. Heterogeneity of PD-L1 expression and relationship with biology of NSCLC. Anticancer Res. 2018;38(7): 3789–3796. doi: 10.21873/anticanres.12662
  • Allen EMV, Miao D, Schilling B et al. Genomic correlates of response to CTLA4 blockade in metastatic melanoma. Science. 2015;9:207–211. doi: 10.1126/ science.aad0095
  • Hendriks LE, Rouleau E and Besse B. Clinical utility of tumor mutational burden in patients with non-small cell lung cancer treated with immunotherapy. Transl Lung Cancer Res 2018;7(6):647–660. doi: 10.21037/tlcr.2018.09.22
  • Büttner R, Longshore JW, López-Ríos F et al. Implementing TMB measurement in clinical practice: considerations and requirements. ESMO Open 2019;4(1):442. doi: 10.1136/esmoopen-2018-000442
  • Le DT et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357(6349):409–413. doi: 10.1126/science.aan6733
  • Subrahmanyam PB, Dong Z, Gusenleitner D et al. Distinct predicitve biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients. J Immunother Cancer 2018;6(1):18. doi: 10.1186/s40425- 018-0328-8
  • Tietze JK, Angelova D, Heppt MV et al. The proportion of circulating CD45RO+CD8+ memory T cells is correlated with clinical response in melanoma patients treated with ipilimumab. Eur J Cancer 2017;75:268–279. doi: 10.1016/j.ejca.2016.12.031
  • Lutz ER, Wu AA, Bigelow E et al. Immunotherapy converts non- immunogenic pancreatic tumours into immunogenic foci of immune regulation. Cancer Immunol Res 2014;2(7):616–631. doi: 10.1158/2326-6066.CIR-14-0027
  • Blank CU, Haanen JB, Ribas A and Schumacher TN. The “cancer immunogram”. Science 2016;658–660. doi: 10.1126/science.aaf2834
  • Cassidy MR, Wolchok RE, Zheng J et al. Neutrophil to lymphocyte ratio is associated with outcome during ipilimumab treatment. EBioMedicine 2017;18:56–61. doi: 10.1016/j.ebiom.2017.03.029
  • Gujar S, Pol JG and Kroemer G. Heating it up: oncolytic viruses make tumours hot and suitable for checkpoint blockade immunotherpies. Oncoimmunology 2018;7(8):e1442169. doi: 10.1080/2162402X.2018.1442169
  • Haanen JBAG. Converting cold into hot tumors by combining immunotherapies. Cell 2017;170(6):1055–1056. doi: 10.1016/j.cell.2017.08.031
  • Kershaw MH, Devaud C, John LB et al. Enhancing immunotherapy using chemotherapy and radiation to modify the tumor microenvironment. Oncoimmunology 201;2(9):e25962. doi: 10.4161/onci.25962
  • Wang Y, Deng W, Li N et al. Combining immunotherapy and radiotherapy for cancer treatment: current challendes and future directions. Front Pharmacol 2018;9:185. doi: 10.3389/fphar.2018.00185
  • Alsaab HO, Sau S, Alzhrani R et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol 2017;8:561. doi: 10.3389/fphar.2017.00561
  • Paz-Ares L, Luft A, Vicente D et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 2018;379(21):2040–2051. doi: 0.1056/NEJMoa1810865

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  • Review on Immuno-Oncology Agents for Cancer Therapy

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Authors

Ganesh G. Dhakad
Ahinsa Institute of Pharmacy, Dondaicha 425408, India
Sangita P. Shirsat
Ahinsa Institute of Pharmacy, Dondaicha 425408, India
Kaveri P. Tambe
Ahinsa Institute of Pharmacy, Dondaicha 425408, India
Vinit Kairnar
Ahinsa Institute of Pharmacy, Dondaicha 425408, India
Ritik. S. Jain
Ahinsa Institute of Pharmacy, Dondaicha 425408, India

Abstract


Until recently, cancer therapy comprised of four main types of treatment: surgery, radiotherapy, chemotherapy and targeted therapy. Over the past decade, immuno-oncology (IO) has emerged as a novel and important approach to cancer treatment through the stimulation of the body’s own immune system to kill cancer cells. This newly recognised method of treating cancer is rapidly developing, with many accelerated approvals by the US Food and Drug Administration and European Medicines Agency in 2019. Several therapeutic classes have emerged within IO, and are the focus of this review article. In particular, the immune checkpoint inhibitors have had remarkable success across multiple malignancies, and are the most well-established therapeutic class of IO agents to date. Biomarker testing for the programmed death-ligand 1 (PD-L1) checkpoint target has been developed and is now obligatory before treatment with pembrolizumab (Keytruda, Merck) when used for non- small-cell lung carcinoma, gastric cancer, head and neck squamous cell carcinoma and cervical cancer, as well as before treatment with atezolizumab (Tecentriq, Roche) when used for urothelial carcinoma. However, ambiguity remains as to the relevance of PD-L1 expression for checkpoint inhibition therapy for other tumour types. More recently, combining IO agents with conventional therapies has been evaluated with some significant improvements in patient outcomes. While IO agents are rapidly changing the standard of care for people with cancer, there are still many challenges to overcome in terms of managing their toxicities and ensuring that healthcare systems, such as the NHS, can afford the high cost of these therapies. The IO pipeline also includes chimeric antigen receptor T-cell therapies and cancer vaccines, both of which show great promise for the future but have their own unique toxicity and cost-effectiveness issues.


Keywords


Biomarkers, Cancer, Immune checkpoint inhibitors, Immune-oncology, Oncology

References