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Current Reviews in Clinical and Experimental Pharmacology

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ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

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Review Article

Immune Checkpoint Inhibitors in the Treatment of Cancer

Author(s): Wissam Zam* and Lina Ali

Volume 17, Issue 2, 2022

Published on: 25 March, 2021

Page: [103 - 113] Pages: 11

DOI: 10.2174/1574884716666210325095022

Price: $65

Abstract

Background: Immunotherapy drugs, known as immune checkpoint inhibitors (ICIs), work by blocking checkpoint proteins from binding with their partner proteins. The two main pathways that are specifically targeted in clinical practice are cytotoxic T-lymphocyte antigen-4 (CTLA- 4) and programmed cell death protein 1 (PD-1) that showed potent immune-modulatory effects through their function as negative regulators of T cell activation.

Methods: In view of the rapid and extensive development of this research field, we conducted a comprehensive review of the literature and updated on the use of CTLA-4, PD-1, and PD-L1 targeted therapy in the treatment of several types of cancer, including melanoma, non-small-cell lung carcinoma, breast cancer, hepatocellular carcinoma, Hodgkin lymphoma, cervical cancer, and head and neck squamous cell carcinoma.

Results: Based on the last updated list released on March 2019, seven ICIs are approved by the FDA, including ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, and cemiplimab.

Conclusion: This review highlighted the most common adverse effects caused by ICIs which affect people in different ways.

Keywords: Immune checkpoint inhibitors, cancer, side effects, CTLA-4, PD-1/PDL-1.

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Graphical Abstract

[1]
Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition. Am J Clin Oncol 2016; 39(1): 98-106.
[http://dx.doi.org/10.1097/COC.0000000000000239] [PMID: 26558876]
[2]
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12(4): 252-64.
[http://dx.doi.org/10.1038/nrc3239] [PMID: 22437870]
[3]
Solinas C, Gombos A, Latifyan S, Piccart-Gebhart M, Kok M, Buisseret L. Targeting immune checkpoints in breast cancer: an update of early results. ESMO Open 2017; 2(5)e000255
[http://dx.doi.org/10.1136/esmoopen-2017-000255] [PMID: 29177095]
[4]
De Velasco G, Je Y, Bossé D, et al. Comprehensive meta-analysis of key immune-related adverse events from CTLA-4 and PD-1/PD-L1 inhibitors in cancer patients. Cancer Immunol Res 2017; 5(4): 312-8.
[http://dx.doi.org/10.1158/2326-6066.CIR-16-0237] [PMID: 28246107]
[5]
Queirolo P, Boutros A, Tanda E, Spagnolo F, Quaglino P. Immune-checkpoint inhibitors for the treatment of metastatic melanoma: a model of cancer immunotherapy. Semin Cancer Biol 2019; 59: 290-7.
[http://dx.doi.org/10.1016/j.semcancer.2019.08.001] [PMID: 31430555]
[6]
Schadendorf D, Hodi FS, Robert C, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 2015; 33(17): 1889-94.
[http://dx.doi.org/10.1200/JCO.2014.56.2736] [PMID: 25667295]
[7]
Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med 2016; 375(19): 1845-55.
[http://dx.doi.org/10.1056/NEJMoa1611299] [PMID: 27717298]
[8]
Butler M, Hamid O, Ribas A, et al. Efficacy of pembrolizumab in patients with advanced mucosal melanoma enrolled in the KEYNOTE-001, 002, and 006 studies. Eur J Cancer 2017; 72: S123.
[http://dx.doi.org/10.1016/S0959-8049(17)30483-5]
[9]
Constantinidou A, Alifieris C, Trafalis DT. Targeting Programmed Cell Death -1 (PD-1) and Ligand (PD-L1): A new era in cancer active immunotherapy. Pharmacol Ther 2019; 194: 84-106.
[http://dx.doi.org/10.1016/j.pharmthera.2018.09.008] [PMID: 30268773]
[10]
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): 785-92.
[http://dx.doi.org/10.1200/JCO.2015.66.1389] [PMID: 28068177]
[11]
Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 2015; 372(21): 2006-17.
[http://dx.doi.org/10.1056/NEJMoa1414428] [PMID: 25891304]
[12]
Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015; 373(1): 23-34.
[http://dx.doi.org/10.1056/NEJMoa1504030] [PMID: 26027431]
[13]
Coit DG, Thompson JA, Albertini MR, et al. Cutaneous melanoma. Version2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2019; 17(4): 367-402.
[http://dx.doi.org/10.6004/jnccn.2019.0018] [PMID: 30959471]
[14]
Hodi FS, Chiarion-Sileni V, Gonzalez R, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol 2018; 19(11): 1480-92.
[http://dx.doi.org/10.1016/S1470-2045(18)30700-9] [PMID: 30361170]
[15]
Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous cell non-small-cell lung cancer. N Engl J Med 2015; 373(2): 123-35.
[http://dx.doi.org/10.1056/NEJMoa1504627] [PMID: 26028407]
[16]
Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in advanced non-squamous non-small-cell lung cancer. N Engl J Med 2015; 373(17): 1627-39.
[http://dx.doi.org/10.1056/NEJMoa1507643] [PMID: 26412456]
[17]
Carbone DP, Reck M, Paz-Ares L, et al. CheckMate 026 Investigators. CheckMate 026 Investigators. First-line nivolumab in stage iv or recurrent non-small-cell lung cancer. N Engl J Med 2017; 376(25): 2415-26.
[http://dx.doi.org/10.1056/NEJMoa1613493] [PMID: 28636851]
[18]
Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2016; 387(10027): 1540-50.
[http://dx.doi.org/10.1016/S0140-6736(15)01281-7] [PMID: 26712084]
[19]
Reck M, Rodríguez-Abreu D, Robinson AG, et al. KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; 375(19): 1823-33.
[http://dx.doi.org/10.1056/NEJMoa1606774] [PMID: 27718847]
[20]
Mok TSK, Wu Y-L, Kudaba I, et al. KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 2019; 393(10183): 1819-30.
[http://dx.doi.org/10.1016/S0140-6736(18)32409-7] [PMID: 30955977]
[21]
Fehrenbacher L, Spira A, Ballinger M, et al. POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 2016; 387(10030): 1837-46.
[http://dx.doi.org/10.1016/S0140-6736(16)00587-0] [PMID: 26970723]
[22]
Rittmeyer A, Barlesi F, Waterkamp D, et al. OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 2017; 389(10066): 255-65.
[http://dx.doi.org/10.1016/S0140-6736(16)32517-X] [PMID: 27979383]
[23]
Vaddepally RK, Kharel P, Pandey R, Garje R, Chandra AB. Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence. Cancers (Basel) 2020; 12(3): 738.
[http://dx.doi.org/10.3390/cancers12030738] [PMID: 32245016]
[24]
Antonia SJ, Villegas A, Daniel D, et al. PACIFIC Investigators. Durvalumab after chemo-radio therapy in stage III non-small-cell lung cancer. N Engl J Med 2017; 377(20): 1919-29.
[http://dx.doi.org/10.1056/NEJMoa1709937] [PMID: 28885881]
[25]
Antonia SJ, Villegas A, Daniel D, et al. PACIFIC Investigators. Overall survival with durvalumab after chemoradio therapy in stage III NSCLC. N Engl J Med 2018; 379(24): 2342-50.
[http://dx.doi.org/10.1056/NEJMoa1809697] [PMID: 30280658]
[26]
Barrett MT, Anderson KS, Lenkiewicz E, et al. Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer. Oncotarget 2015; 6(28): 26483-93.
[http://dx.doi.org/10.18632/oncotarget.4494] [PMID: 26317899]
[27]
Mittendorf EA, Philips AV, Meric-Bernstam F, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res 2014; 2(4): 361-70.
[http://dx.doi.org/10.1158/2326-6066.CIR-13-0127] [PMID: 24764583]
[28]
Bozeman EN, He S, Shafizadeh Y, Selvaraj P. Therapeutic efficacy of PD-L1 blockade in a breast cancer model is enhanced by cellular vaccines expressing B7-1 and glycolipid-anchored IL-12. Hum Vaccin Immunother 2016; 12(2): 421-30.
[http://dx.doi.org/10.1080/21645515.2015.1076953] [PMID: 26308597]
[29]
Sabatier R, Finetti P, Mamessier E, et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 2015; 6(7): 5449-64.
[http://dx.doi.org/10.18632/oncotarget.3216] [PMID: 25669979]
[30]
Ali HR, Glont SE, Blows FM, et al. PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol 2015; 26(7): 1488-93.
[http://dx.doi.org/10.1093/annonc/mdv192] [PMID: 25897014]
[31]
Su M, Huang C-X, Dai A-P. Immune checkpoint inhibitors: therapeutic tools for breast cancer. Asian Pac J Cancer Prev 2016; 17(3): 905-10.
[http://dx.doi.org/10.7314/APJCP.2016.17.3.905] [PMID: 27039716]
[32]
Hassannia H, Ghasemi Chaleshtari M, Atyabi F, et al. Blockage of immune checkpoint molecules increases T-cell priming potential of dendritic cell vaccine. Immunology 2020; 159(1): 75-87.
[http://dx.doi.org/10.1111/imm.13126] [PMID: 31587253]
[33]
Wang M, Yao L-C, Cheng M, et al. Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy. FASEB J 2018; 32(3): 1537-49.
[http://dx.doi.org/10.1096/fj.201700740R] [PMID: 29146734]
[34]
Schmid P, Cruz C, Braiteh FS, et al. Atezolizumab in metastatic TNBC (mTNBC): Long-term clinical outcomes and biomarker analyses 2017; 2986.
[35]
Emens LA, Braiteh FS, Cassier P, et al. Inhibition of PD-L1 byMPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer. Proc AACR 106th Annual Meeting. Abstract 2859
[36]
Zou Y, Zou X, Zheng S, et al. Efficacy and predictive factors of immune checkpoint inhibitors in metastatic breast cancer: a systematic review and meta-analysis. Ther Adv Med Oncol 2020; 121758835920940928
[http://dx.doi.org/10.1177/1758835920940928] [PMID: 32874208]
[37]
Vonderheide RH, LoRusso PM, Khalil M, et al. Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clin Cancer Res 2010; 16(13): 3485-94.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-0505] [PMID: 20479064]
[38]
El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012; 142(6): 1264-1273.e1.
[http://dx.doi.org/10.1053/j.gastro.2011.12.061] [PMID: 22537432]
[39]
Voutsadakis IA. PD-1 inhibitors monotherapy in hepatocellular carcinoma: Meta-analysis and systematic review. Hepatobiliary Pancreat Dis Int 2019; 18(6): 505-10.
[http://dx.doi.org/10.1016/j.hbpd.2019.09.007] [PMID: 31551142]
[40]
Greten TF, Lai CW, Li G, Staveley-O’Carroll KF. Targeted and immune-based therapies for hepatocellular carcinoma. Gastroenterology 2019; 156(2): 510-24.
[http://dx.doi.org/10.1053/j.gastro.2018.09.051] [PMID: 30287171]
[41]
El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017; 389(10088): 2492-502.
[http://dx.doi.org/10.1016/S0140-6736(17)31046-2] [PMID: 28434648]
[42]
Zhu AX, Finn RS, Edeline J, et al. KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol 2018; 19(7): 940-52.
[http://dx.doi.org/10.1016/S1470-2045(18)30351-6] [PMID: 29875066]
[43]
Finn RS, Ryoo BY, Merle P, et al. KEYNOTE-240 investigators. Keynote-240 investigators. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial. J Clin Oncol 2020; 38(3): 193-202.
[http://dx.doi.org/10.1200/JCO.19.01307] [PMID: 31790344]
[44]
Ansell SM. Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management. Am J Hematol 2018; 93(5): 704-15.
[http://dx.doi.org/10.1002/ajh.25071] [PMID: 29634090]
[45]
Armand P, Shipp MA, Ribrag V, et al. Programmed death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol 2016; 34(31): 3733-9.
[http://dx.doi.org/10.1200/JCO.2016.67.3467] [PMID: 27354476]
[46]
Upadhyay R, Hammerich L, Peng P, Brown B, Merad M, Brody JD. Lymphoma: immune evasion strategies. Cancers (Basel) 2015; 7(2): 736-62.
[http://dx.doi.org/10.3390/cancers7020736] [PMID: 25941795]
[47]
Green MR, Monti S, Rodig SJ, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood 2010; 116(17): 3268-77.
[http://dx.doi.org/10.1182/blood-2010-05-282780] [PMID: 20628145]
[48]
Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 2015; 372(4): 311-9.
[http://dx.doi.org/10.1056/NEJMoa1411087] [PMID: 25482239]
[49]
Younes A, Santoro A, Shipp M, et al. Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol 2016; 17(9): 1283-94.
[http://dx.doi.org/10.1016/S1470-2045(16)30167-X] [PMID: 27451390]
[50]
Armand P, Engert A, Younes A, et al. Nivolumab for relapsed/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm Phase II CheckMate 205 Trial. J Clin Oncol 2018; 36(14): 1428-39.
[http://dx.doi.org/10.1200/JCO.2017.76.0793] [PMID: 29584546]
[51]
Chen R, Zinzani PL, Fanale MA, et al. KEYNOTE-087. KeyNote-087. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol 2017; 35(19): 2125-32.
[http://dx.doi.org/10.1200/JCO.2016.72.1316] [PMID: 28441111]
[52]
Schiffman M, Doorbar J, Wentzensen N, et al. Carcinogenic human papillomavirus infection. Nat Rev Dis Primers 2016; 2: 16086.
[http://dx.doi.org/10.1038/nrdp.2016.86] [PMID: 27905473]
[53]
Chan CK, Aimagambetova G, Ukybassova T, Kongrtay K, Azizan A. Human papillomavirus infection and cervical cancer: Epidemiology, screening, and vaccination—review of current perspectives. J Oncol 2019; 20193257939
[http://dx.doi.org/10.1155/2019/3257939] [PMID: 31687023]
[54]
Liu Z, Zhou H, Wang W, Fu YX, Zhu M. A novel dendritic cell targeting HPV16 E7 synthetic vaccine in combination with PD-L1 blockade elicits therapeutic antitumor immunity in mice. OncoImmunology 2016; 5(6)e1147641
[http://dx.doi.org/10.1080/2162402X.2016.1147641] [PMID: 27471615]
[55]
Frenel J-S, Tourneau CL, O’Neil BH, et al. Pembrolizumab in patients with advanced cervical squamous cell cancer: preliminary results from the phase Ib KeyNote-028 study. J Clin Oncol 2016; 34: 5515.
[http://dx.doi.org/10.1200/JCO.2016.34.15_suppl.5515]
[56]
Shibata T, Lieblong BJ, Sasagawa T, Nakagawa M. The promise of combining cancer vaccine and checkpoint blockade for treating HPV-related cancer. Cancer Treat Rev 2019; 78: 8-16.
[http://dx.doi.org/10.1016/j.ctrv.2019.07.001] [PMID: 31302573]
[57]
Minion LE, Tewari KS. Cervical cancer - State of the science: From angiogenesis blockade to checkpoint inhibition. Gynecol Oncol 2018; 148(3): 609-21.
[http://dx.doi.org/10.1016/j.ygyno.2018.01.009] [PMID: 29666026]
[58]
Liu C, Lu J, Tian H, et al. Increased expression of PD‑L1 by the human papillomavirus 16 E7 oncoprotein inhibits anticancer immunity. Mol Med Rep 2017; 15(3): 1063-70.
[http://dx.doi.org/10.3892/mmr.2017.6102] [PMID: 28075442]
[59]
Frenel J-S, Le Tourneau C, O’Neil B, et al. Safety and Efficacy of pembrolizumab in advanced, programmed death ligand 1–positive cervical cancer: Results from the phase Ib KeyNote-028 trial. J Clin Oncol 2017; 35(36): 4035-41.
[http://dx.doi.org/10.1200/JCO.2017.74.5471] [PMID: 29095678]
[60]
Fashoyin-Aje L, Donoghue M, Chen H, et al. FDA approval summary: Pembrolizumab for recurrent locally advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma expressing PD-L1. Oncologist 2019; 24(1): 103-9.
[http://dx.doi.org/10.1634/theoncologist.2018-0221] [PMID: 30120163]
[61]
Hollebecque A, Meyer T, Moore KN, et al. An open-label, multicohort, phase I/II study of nivolumab in patients with virus-associated tumors (Check-Mate 358): efficacy and safety in recurrent or metastatic(R/M) cervical, vaginal, and vulvar cancers. J Clin Oncol 2017; 35: 5504.
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.5504]
[62]
Kagabu M, Nagasawa T, Sato C, et al. Immunotherapy for uterine cervical cancer using checkpoint inhibitors: future directions. Int J Mol Sci 2020; 21(7): 1-12.
[http://dx.doi.org/10.3390/ijms21072335] [PMID: 32230938]
[63]
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2): 87-108.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[64]
Solomon B, Young RJ, Rischin D. Head and neck squamous cell carcinoma: Genomics and emerging biomarkers for immunomodulatory cancer treatments. Semin Cancer Biol 2018; 52(Pt 2): 228-40.
[http://dx.doi.org/10.1016/j.semcancer.2018.01.008] [PMID: 29355614]
[65]
Rischin D, Young RJ, Fisher R, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol 2010; 28(27): 4142-8.
[http://dx.doi.org/10.1200/JCO.2010.29.2904] [PMID: 20697079]
[66]
Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010; 363(1): 24-35.
[http://dx.doi.org/10.1056/NEJMoa0912217] [PMID: 20530316]
[67]
Busch CJ, Kriegs M, Laban S, et al. HPV-positive HNSCC cell lines but not primary human fibroblasts are radiosensitized by the inhibition of Chk1. Radiother Oncol 2013; 108(3): 495-9.
[http://dx.doi.org/10.1016/j.radonc.2013.06.035] [PMID: 23932155]
[68]
Seiwert TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016; 17(7): 956-65.
[http://dx.doi.org/10.1016/S1470-2045(16)30066-3] [PMID: 27247226]
[69]
Chow LQM, Haddad R, Gupta S, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: Results from the phase ib KEYNOTE-012 expansion cohort. J Clin Oncol 2016; 34(32): 3838-45.
[http://dx.doi.org/10.1200/JCO.2016.68.1478] [PMID: 27646946]
[70]
Bauml J, Seiwert TY, Pfister DG, et al. Pembrolizumab for platinum – and cetuximab-refractory head and neck cancer: results from a single-arm phase II study. J Clin Oncol 2017; 35(14): 1542-9.
[http://dx.doi.org/10.1200/JCO.2016.70.1524] [PMID: 28328302]
[71]
Rischin D, Harrington KJ, Greil R, et al. Protocol-specified final analysis of the phase 3 KEYNOTE-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). J Clin Oncol 2019; 37(15)
[http://dx.doi.org/10.1200/JCO.2019.37.15_suppl.6000]
[72]
Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med 2016; 375(19): 1856-67.
[http://dx.doi.org/10.1056/NEJMoa1602252] [PMID: 27718784]
[73]
Zandberg D, Algazi A, Jimeno A, et al. Durvalumab for recurrent/metastatic (R/M) head and neck squamous cell carcinoma(HNSCC): Preliminary results from a single-arm, phase 2 study. Ann Oncol 2017; 28(5)mdx374
[http://dx.doi.org/10.1093/annonc/mdx374]
[74]
Bahleda R, Braiteh FS, Balmanoukian AS, et al. Long-term safety and clinical outcomes of atezolizumab in head and neck cancer: Phase Ia trial results. Ann Oncol 2017; 28(5): 372-94.
[http://dx.doi.org/10.1093/annonc/mdx374.001a]
[75]
Teufel A, Zhan T, Härtel N, Bornschein J, Ebert MP, Schulte N. Management of immune related adverse events induced by immune checkpoint inhibition. Cancer Lett 2019; 456: 80-7.
[http://dx.doi.org/10.1016/j.canlet.2019.04.018] [PMID: 31051213]
[76]
Bertrand A, Kostine M, Barnetche T, Truchetet ME, Schaeverbeke T. Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis. BMC Med 2015; 13: 211.
[http://dx.doi.org/10.1186/s12916-015-0455-8] [PMID: 26337719]
[77]
Maughan BL, Bailey E, Gill DM, Agarwal N. Incidence of immune-related adverse events with program death receptor-1- and program death receptor-1 ligand directed therapies in genitourinary cancers. Front Oncol 2017; 7: 56.
[http://dx.doi.org/10.3389/fonc.2017.00056] [PMID: 28421161]
[78]
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): 2443-54.
[http://dx.doi.org/10.1056/NEJMoa1200690] [PMID: 22658127]
[79]
Quan Qiu W, Rong X. Immunotherapy-related adverse events (irAEs): extraction from FDA drug labels and comparative analysis. JAMIA open 2019; 2(1): 173-8.
[80]
Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011; 364(26): 2517-26.
[http://dx.doi.org/10.1056/NEJMoa1104621] [PMID: 21639810]
[81]
Chen TW, Razak AR, Bedard PL, Siu LL, Hansen AR. A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors. Ann Oncol 2015; 26(9): 1824-9.
[http://dx.doi.org/10.1093/annonc/mdv182] [PMID: 25888611]
[82]
Voskens CJ, Goldinger SM, Loquai C, et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. PLoS One 2013; 8(1)e53745
[http://dx.doi.org/10.1371/journal.pone.0053745] [PMID: 23341990]
[83]
Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363(8): 711-23.
[http://dx.doi.org/10.1056/NEJMoa1003466] [PMID: 20525992]
[84]
Minkis K, Garden BC, Wu S, Pulitzer MP, Lacouture ME. The risk of rash associated with ipilimumab in patients with cancer: a systematic review of the literature and meta-analysis. J Am Acad Dermatol 2013; 69(3): e121-8.
[http://dx.doi.org/10.1016/j.jaad.2012.12.963] [PMID: 23357570]
[85]
Sibaud V. Dermatologic reactions to immune checkpoint inhibitors: Skin toxicities and immunotherapy. Am J Clin Dermatol 2018; 19(3): 345-61.
[http://dx.doi.org/10.1007/s40257-017-0336-3] [PMID: 29256113]
[86]
Cubero DIG, Abdalla BMZ, Schoueri J, et al. Cutaneous side effects of molecularly targeted therapies for the treatment of solid tumors. Drugs Context 2018; 7212516
[http://dx.doi.org/10.7573/dic.212516] [PMID: 30038659]
[87]
Collins LK, Chapman MS, Carter JB, Samie FH. Cutaneous adverse effects of the immune checkpoint inhibitors. Curr Probl Cancer 2017; 41(2): 125-8.
[http://dx.doi.org/10.1016/j.currproblcancer.2016.12.001] [PMID: 28190531]
[88]
Zhou S, Khanal S, Zhang H. Risk of immune-related adverse events associated with ipilimumab-plus-nivolumab and nivolumab therapy in cancer patients. Ther Clin Risk Manag 2019; 15: 211-21.
[http://dx.doi.org/10.2147/TCRM.S193338] [PMID: 30774357]
[89]
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: 70-6.
[http://dx.doi.org/10.1016/j.ctrv.2017.06.002] [PMID: 28689073]
[90]
Wang DY, Salem JE, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol 2018; 4(12): 1721-8.
[http://dx.doi.org/10.1001/jamaoncol.2018.3923] [PMID: 30242316]
[91]
Jenkins RW, Barbie DA, Flaherty KT. Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer 2018; 118(1): 9-16.
[http://dx.doi.org/10.1038/bjc.2017.434] [PMID: 29319049]
[92]
Veldman J, Visser L, Berg AVD, Diepstra A. Primary and acquired resistance mechanisms to immune checkpoint inhibition in Hodgkin lymphoma. Cancer Treat Rev 2020; 82101931
[http://dx.doi.org/10.1016/j.ctrv.2019.101931] [PMID: 31756590]
[93]
Pitt JM, Vétizou M, Daillère R, et al. Resistance mechanisms to immune-checkpoint blockade in cancer: Tumor-intrinsic and-extrinsic factors. Immunity 2016; 44(6): 1255-69.
[http://dx.doi.org/10.1016/j.immuni.2016.06.001] [PMID: 27332730]
[94]
Zaretsky JM, Garcia-Diaz A, Shin DS, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med 2016; 375(9): 819-29.
[http://dx.doi.org/10.1056/NEJMoa1604958] [PMID: 27433843]
[95]
Tran E, Robbins PF, Lu YC, et al. T-cell transfer therapy targeting mutant KRAS in cancer. N Engl J Med 2016; 375(23): 2255-62.
[http://dx.doi.org/10.1056/NEJMoa1609279] [PMID: 27959684]
[96]
Schoenfeld AJ, Hellmann MD. Acquired resistance to immune checkpoint inhibitors. Cancer Cell 2020; 37(4): 443-55.
[http://dx.doi.org/10.1016/j.ccell.2020.03.017] [PMID: 32289269]
[97]
Qian F-F, Han B-H. Mechanisms of resistance to immune checkpoint inhibitors and strategies to reverse drug resistance in lung cancer. Chin Med J (Engl) 2020; 133(20): 2444-55.
[http://dx.doi.org/10.1097/CM9.0000000000001124] [PMID: 32969861]
[98]
Saleh R, Elkord E. Treg-mediated acquired resistance to immune checkpoint inhibitors. Cancer Lett 2019; 457: 168-79.
[http://dx.doi.org/10.1016/j.canlet.2019.05.003] [PMID: 31078738]
[99]
Zong L, Mo S, Yu S, et al. Expression of the immune checkpoint VISTA in breast cancer. Cancer Immunol Immunother 2020; 69(8): 1437-46.
[http://dx.doi.org/10.1007/s00262-020-02554-3] [PMID: 32266446]

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