364
Views
9
CrossRef citations to date
0
Altmetric
Review

Advances in the pharmacotherapeutic management of esophageal squamous cell carcinoma

&
Pages 93-107 | Received 17 Jun 2020, Accepted 18 Aug 2020, Published online: 09 Oct 2020

References

  • Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
  • Abnet CC, Arnold M, Wei W-Q Epidemiology of Esophageal Squamous Cell Carcinoma. Gastroenterology. 2018;154(2):360–373.
  • Zhang Y Epidemiology of esophageal cancer. World J Gastroenterol. 2013;19(34):5598–5606.
  • He H, Chen N, Hou Y, et al. Trends in the incidence and survival of patients with esophageal cancer: A SEER database analysis. Thorac Cancer 2020 May;11(5):1121–1128.
  • Xie SH, Lagergren J Risk factors for oesophageal cancer. Best Pract Res Clin Gastroenterol. 2018 Oct-Dec;36–37:3–8
  • Abnet CC, Corley DA, Freedman ND, et al. Diet and upper gastrointestinal malignancies. Gastroenterology. 2015 May;148(6):1234–1243.e4.
  • Kim J, Bowlby R, Mungall A, et al. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017 Jan 12;541(7636):169–175.“TCGA analysis of molecular alterations in ESCC and EAC along with differences.
  • Bandla S, Pennathur A, Luketich JD, et al. Comparative genomics of esophageal adenocarcinoma and squamous cell carcinoma. Ann Thorac Surg 2012 Apr;93(4):1101–1106.
  • Gao YB, Chen ZL, Li JG, et al. Genetic landscape of esophageal squamous cell carcinoma. Nat Genet 2014 Oct;46(10):1097–1102.
  • Lin DC, Hao JJ, Nagata Y, et al. Genomic and molecular characterization of esophageal squamous cell carcinoma. Nat Genet 2014 May;46(5):467–473.
  • Qin HD, Liao XY, Chen YB, et al. Genomic characterization of esophageal squamous cell carcinoma reveals critical genes underlying tumorigenesis and poor prognosis. Am J Hum Genet. 2016 Apr 7;98(4):709–727.
  • Sawada G, Niida A, Uchi R, et al. Genomic landscape of esophageal squamous cell carcinoma in a Japanese population. Gastroenterology. 2016 May;150(5):1171–1182.
  • Song Y, Li L, Ou Y, et al. Identification of genomic alterations in oesophageal squamous cell cancer. Nature. 2014 May 1;509(7498):91–95.
  • Zhang L, Zhou Y, Cheng C, et al. Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma. Am J Hum Genet. 2015 Apr 2;96(4):597–611.
  • Ajani JA, D’Amico TA, Bentrem DJ, et al. Esophageal and esophagogastric junction cancers, Version 2.2019, NCCN Clin Pract Guidelines Oncol. 2019;17(7):855.
  • Lordick F, Mariette C, Haustermans K, et al. Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016 Sep;27(suppl 5):v50–v57.
  • Booka E, Takeuchi H, Kitagawa Y Esophageal cancer practice guidelines in Japan. In: Ando N, editor. Esophageal squamous cell carcinoma: diagnosis and treatment. Singapore: Springer Singapore; 2020. p. 131–147.
  • van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074–2084.
  • Tepper J, Krasna MJ, Niedzwiecki D, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008 Mar 1;26(7):1086–1092.
  • Kato K, Muro K, Minashi K, et al. Phase II study of chemoradiotherapy with 5-fluorouracil and cisplatin for stage II-III esophageal squamous cell carcinoma: JCOG trial (JCOG 9906). Int J Radiat Oncol Biol Phys. 2011 Nov 1;81(3):684–690.
  • Ito Y, TAKEUCHI H, Ogawa G, et al. A single-arm confirmatory study of definitive chemoradiotherapy (dCRT) including salvage treatment in patients (pts) with clinical (c) stage II/III esophageal carcinoma (EC) (JCOG0909). J clin oncol. 2018;36(15_suppl):4051.
  • Klevebro F, Alexandersson von Döbeln G, Wang N, et al. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol. 2016 Apr;27(4):660–667.
  • Mayanagi S, Irino T, Kawakubo H, et al. Neoadjuvant treatment strategy for locally advanced thoracic esophageal cancer. Ann Gastroenterol Surg 2019 May;3(3):269–275.
  • Nakamura K, Kato K, Igaki H, et al. Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study). Jpn J Clin Oncol. 2013 Jul;43(7):752–755.
  • Fujita H, Kakegawa T, Yamana H, et al. Mortality and morbidity rates, postoperative course, quality of life, and prognosis after extended radical lymphadenectomy for esophageal cancer. Comparison of three-field lymphadenectomy with two-field lymphadenectomy. Ann Surg 1995 Nov;222(5):654–662.
  • Kawakubo H Surgery transthoracic esophagectomy. In: Ando N, editor. Esophageal squamous cell carcinoma: diagnosis and treatment. Singapore: Springer Singapore; 2020. p. 161–175.
  • Shim YM, Kim HK, Kim K Comparison of survival and recurrence pattern between two-field and three-field lymph node dissections for upper thoracic esophageal squamous cell carcinoma. J Thorac Oncol 2010 May;5(5):707–712.
  • Stahl M, Stuschke M, Lehmann N, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol. 2005 Apr 1;23(10):2310–2317.
  • Vellayappan BA, Soon YY, Ku GY, et al. Chemoradiotherapy versus chemoradiotherapy plus surgery for esophageal cancer. Cochrane Database Syst Rev. 2017 Aug 22;8(8):Cd010511.
  • Herskovic A, Martz K, al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992 Jun 11;326(24):1593–1598.
  • Conroy T, Galais M-P, Raoul J-L, et al. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014;15(3):305–314.
  • Ter Veer E, Haj Mohammad N, van Valkenhoef G, et al. The efficacy and safety of first-line chemotherapy in advanced esophagogastric cancer: a network meta-analysis. J Natl Cancer Inst 2016 Oct;108(10).
  • Janmaat VT, Steyerberg EW, van der Gaast A, et al. Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer. Cochrane Database Syst Rev. 2017 Nov 28;11(11):Cd004063.
  • Ter Veer E, Haj Mohammad N, van Valkenhoef G, et al. Second- and third-line systemic therapy in patients with advanced esophagogastric cancer: a systematic review of the literature. Cancer Metastasis Rev 2016 Sep;35(3):439–456.
  • Wang Q, Zhu H, Xiao Z, et al. Expression of epidermal growth factor receptor is an independent prognostic factor for esophageal squamous cell carcinoma. World J Surg Oncol 2013 Oct 16;11:278.
  • Song J, Shi W, Zhang Y, et al. Epidermal growth factor receptor and B7-H3 expression in esophageal squamous tissues correlate to patient prognosis. OncoTargets Therapy 2016;9:6257–6263.
  • FDA. ERBITUX (cetuximab) [Website]. 2019 [cited 2020 May 24]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125084s273lbl.pdf
  • FDA. VECTIBIX (panitumumab). 2017. [cited 2020 May 24].
  • Rades D, Moehler MH, Debus J, et al. LEOPARD-II: A randomized phase II study of radiochemotherapy (RCT) with 5FU and cisplatin plus/minus cetuximab (Cet) in unresectable locally advanced esophageal cancer (LAEC). J clin oncol. 2014;32(15_suppl):4081.
  • Meng X, Wang J, Sun X, et al. Cetuximab in combination with chemoradiotherapy in Chinese patients with non-resectable, locally advanced esophageal squamous cell carcinoma: a prospective, multicenter phase II trail. Radiother Oncol 2013 Nov;109(2):275–280.
  • Lledo G, Huguet F, Chibaudel B, et al. Chemoradiotherapy with FOLFOX plus cetuximab in locally advanced oesophageal cancer: the GERCOR phase II trial ERaFOX. Euro J Cancer (Oxford, England: 1990) 2016 Mar;56:115–121.
  • Chen Y, Wu X, Bu S, et al. Promising outcomes of definitive chemoradiation and cetuximab for patients with esophageal squamous cell carcinoma. Cancer Sci. 2012;103(11):1979–1984.
  • De Vita F, Orditura M, Martinelli E, et al. A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer. Br J Cancer. 2011 Feb 1;104(3):427–432.
  • Crosby T, Hurt CN, Falk S, et al. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial. Lancet Oncol. 2013 Jun;14(7):627–637.
  • Suntharalingam M, Winter K, Ilson D, et al. Effect of the addition of cetuximab to paclitaxel, cisplatin, and radiation therapy for patients with esophageal cancer: the nrg oncology RTOG 0436 phase 3 randomized clinical trial. JAMA Oncol. 2017 Nov 1;3(11):1520–1528.
  • Ruhstaller T, Thuss-Patience P, Hayoz S, et al. Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08). Ann Oncol. 2018 Jun 1;29(6):1386–1393.
  • Ruhstaller T, Pless M, Dietrich D, et al. Cetuximab in combination with chemoradiotherapy before surgery in patients with resectable, locally advanced esophageal carcinoma: a prospective, multicenter phase IB/II Trial (SAKK 75/06). J Clin Oncol. 2011 Feb 20;29(6):626–631.
  • Lorenzen S, Schuster T, Porschen R, et al. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009 Oct;20(10):1667–1673.
  • Janjigian YY, Ku GY, Campbell JC, et al. Phase II trial of cetuximab plus cisplatin and irinotecan in patients with cisplatin and irinotecan-refractory metastatic esophagogastric cancer. Am J Clin Oncol 2014 Apr;37(2):126–130.
  • Tebbutt NC, Parry MM, Zannino D, et al. Docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophagogastric cancer: the AGITG ATTAX2 trial. Br J Cancer. 2013 Mar 5;108(4):771–774.
  • Huang ZH, Ma XW, Zhang J, et al. Cetuximab for esophageal cancer: an updated meta-analysis of randomized controlled trials. BMC Cancer. 2018 Nov 26;18(1):1170.
  • Moehler M, Maderer A, Thuss-Patience PC, et al. Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER). Ann Oncol. 2020 Feb;31(2):228–235.
  • Ramakrishnan MS, Eswaraiah A, Crombet T, et al. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. MAbs. 2009 Jan-Feb;1(1):41–48.
  • Mazorra Z, Chao L, Lavastida A, et al. Nimotuzumab: beyond the EGFR signaling cascade inhibition. Semin Oncol 2018 Jan;45(1–2):18–26.
  • Jing W, Yan W, Liu Y, et al. Slight advantages of nimotuzumab versus cetuximab plus concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma. Cancer Biol Ther. 2019;20(8):1121–1126.
  • de Castro Junior G, Segalla JG, de Azevedo SJ, et al. A randomised phase II study of chemoradiotherapy with or without nimotuzumab in locally advanced oesophageal cancer: NICE trial. Euro J Cancer (Oxford, England: 1990) 2018 Jan;88:21–30.
  • Liang J, E M, Wu G, et al. Nimotuzumab combined with radiotherapy for esophageal cancer: preliminary study of a Phase II clinical trial. OncoTargets Therapy 2013;6:1589–1596.
  • Zhang X, Jia J, Lu M, et al. Nimotuzumab plus paclitaxel and cisplatin as 1st line treatment for unresectable esophageal squamous cell carcinoma: long term follow-up of survival in a phase II study. J clin oncol. 2017;35(15_suppl):e15573–e15573.
  • Lu M, Wang X, Shen L, et al. Nimotuzumab plus paclitaxel and cisplatin as the first line treatment for advanced esophageal squamous cell cancer: A single centre prospective phase II trial. Cancer Sci 2016 Apr;107(4):486–490.
  • FDA. IRESSA (gefitinib). 2015 [cited 2020 May 24].
  • FDA. TARCEVA (erlotinib). 2016 [cited 2020 May 24].
  • Imai K, Takaoka A Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer. 2006 Sept 01;6(9):714–727.
  • Dassonville O, Bozec A, Fischel JL, et al. EGFR targeting therapies: monoclonal antibodies versus tyrosine kinase inhibitors: similarities and differences. Crit Rev Oncol Hematol. 2007 apr 01;62(1):53–61.
  • Dutton SJ, Ferry DR, Blazeby JM, et al. Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial. Lancet Oncol. 2014 Jul;15(8):894–904.
  • Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA, et al. Predictive factors for outcome in a phase II study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol. 2006 Apr1;24(10):1612–1619.
  • Adelstein DJ, Rodriguez CP, Rybicki LA, et al. A phase II trial of gefitinib for recurrent or metastatic cancer of the esophagus or gastroesophageal junction. Invest New Drugs 2012 Aug;30(4):1684–1689.
  • Petty RD, Dahle-Smith A, Stevenson DAJ, et al. Gefitinib and EGFR gene copy number aberrations in esophageal cancer. J Clin Oncol. 2017 Jul 10;35(20):2279–2287.
  • Sohal DP, Rice TW, Rybicki LA, et al. Gefitinib in definitive management of esophageal or gastroesophageal junction cancer: a retrospective analysis of two clinical trials. Dis Esophagus 2015 Aug-Sep; 28(6):547–551.
  • Xu Y, Zheng Y, Sun X, et al. Concurrent radiotherapy with gefitinib in elderly patients with esophageal squamous cell carcinoma: preliminary results of a phase II study. Oncotarget. 2015 Nov 10;6(35):38429–38439.
  • Iyer R, Chhatrala R, Shefter T, et al. Erlotinib and radiation therapy for elderly patients with esophageal cancer - clinical and correlative results from a prospective multicenter phase 2 trial. Oncology. 2013;85(1):53–58.
  • Song T, Du D, Zhang X, et al. Comparative study of radiotherapy plus erlotinib versus chemoradiotherapy for elderly patients with esophageal cancer: a propensity score-matched analysis. Dis Esophagus. 2017 Sep 1;30(9):1–10.
  • Zhao C, Lin L, Liu J, et al. A phase II study of concurrent chemoradiotherapy and erlotinib for inoperable esophageal squamous cell carcinoma. Oncotarget. 2016 Aug 30;7(35):57310–57316.
  • Wu SX, Wang LH, Luo HL, et al. Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer. Euro J Cancer (Oxford, England: 1990) 2018 Apr;93:99–107.
  • Ilson DH, Kelsen D, Shah M, et al. A phase 2 trial of erlotinib in patients with previously treated squamous cell and adenocarcinoma of the esophagus. Cancer. 2011 Apr 1;117(7):1409–1414.
  • Horgan AM, Darling G, Wong R, et al. Adjuvant sunitinib following chemoradiotherapy and surgery for locally advanced esophageal cancer: a phase II trial. Dis Esophagus 2016 Nov;29(8):1152–1158.
  • Janjigian YY, Vakiani E, Ku GY, et al. Phase II trial of sorafenib in patients with chemotherapy refractory metastatic esophageal and gastroesophageal (GE) junction cancer. PLoS One. 2015;10(8):e0134731.
  • Chu L, Liang F, Zhang J, et al. A phase II study of apatinib in patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC). Ann Oncol. 2019;30:ix177.
  • Zhao J, Lei J, Yu J, et al. Clinical efficacy and safety of apatinib combined with S-1 in advanced esophageal squamous cell carcinoma. Invest New Drugs. 2020 Apr;38(2):500–506.
  • Huang J, Xiao J, Fang W, et al. Anlotinib in chemotherapy-refractory metastatic esophageal squamous cell carcinoma (ESCC): A randomized, double-blind, multicenter phase II trial. J clin oncol. 2019;37(4_suppl):95.
  • Wang Z, editor A phase II study of rh-endostatin combined with paclitaxel and nedaplatin in treating patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC). 2020; ASCO Virtual Scientific Program: American Society of Clinical Oncology.
  • Xu X, Mao W, Chen Q, et al. Endostar, a modified recombinant human endostatin, suppresses angiogenesis through inhibition of Wnt/β-catenin signaling pathway. PLoS One. 2014;9(9):e107463.
  • Ling Y, Yang Y, Lu N, et al. Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells. Biochem Biophys Res Commun. 2007 Sep 14;361(1):79–84.
  • Song Q, Liu Y, Jiang D, et al. High amplification of FGFR1 gene is a delayed poor prognostic factor in early stage ESCC patients. Oncotarget. 2017 Sep 26;8(43):74539–74553.
  • Karasic TB, O’Hara MH, Teitelbaum UR, et al. Phase II trial of palbociclib in patients with advanced esophageal or gastric cancer. J clin oncol. 2018;36(4_suppl):68.
  • Zhou J, Wu Z, Wong G, et al. CDK4/6 or MAPK blockade enhances efficacy of EGFR inhibition in oesophageal squamous cell carcinoma. Nat Commun 2017 Jan 6;8:13897.
  • Ma S, Paiboonrungruan C, Yan T, et al. Targeted therapy of esophageal squamous cell carcinoma: the NRF2 signaling pathway as target. Ann N Y Acad Sci. 2018 Dec;1434(1):164–172.
  • 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):711–723.
  • Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2014;372(4):320–330.
  • 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.
  • Buchbinder EI, Desai ACTLA 4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016 Feb;39(1):98–106.
  • Wei SC, Duffy CR, Allison JP Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 2018;8(9):1069–1086.
  • Zou W, Wolchok JD, Chen L PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci Transl Med. 2016 Mar 2;8(328):328rv4.
  • FDA. KEYTRUDA® (pembrolizumab) 2020 [cited 2020 May 30].
  • FDA. LIBTAYO® (cemiplimab-rwlc). 2019 [cited 2020 May 30].
  • FDA. BAVENCIO® (avelumab). 2019 [cited 2020 May 30].
  • FDA. TECENTRIQ® (atezolizumab). 2020 [cited 2020 May 30].
  • FDA. IMFINZI® (durvalumab). 2020 [cited 2020 May 30].
  • Wang DY, Johnson DB, Davis EJ Toxicities associated with PD-1/PD-L1 blockade. Cancer J. 2018 Jan/Feb;24(1):36–40.
  • Gibney GT, Weiner LM, Atkins MB Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol 2016 Dec; 17(12):e542–e551.
  • Havel JJ, Chowell D, Chan TA The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer 2019 Mar;19(3):133–150.
  • FDA. OPDIVO (nivolumab) 2020 [cited 2020 May 30].
  • FDA. YERVOY (ipilimumab). 2020 [cited 2020 May 30].
  • Vrána D, Matzenauer M, Č N, et al. From tumor immunology to immunotherapy in gastric and esophageal cancer. Int J Mol Sci 2018 Dec 20;20(1).
  • Fessas P, Lee H, Ikemizu S, et al. A molecular and preclinical comparison of the PD-1-targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab. Semin Oncol. 2017 Apr;44(2):136–140.
  • Shah MA, Kojima T, Hochhauser D, et al. Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: the phase 2 KEYNOTE-180 study. JAMA Oncol. 2019;5(4):546–550.
  • Shah MA, Adenis A, Enzinger PC, et al. Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: phase 3 KEYNOTE-181 study. J clin oncol. 2019;37(15_suppl):4010.
  • Chen J, Luo S, Qin S, et al. Pembrolizumab vs chemotherapy in patients with advanced/metastatic adenocarcinoma (AC) or squamous cell carcinoma (SCC) of the esophagus as second-line therapy: analysis of the Chinese subgroup in KEYNOTE-181. Ann Oncol 2019;30:v294.
  • Kudo T, Hamamoto Y, Kato K, et al. Nivolumab treatment for oesophageal squamous-cell carcinoma: an open-label, multicentre, phase 2 trial. Lancet Oncol. 2017;18(5):631–639.
  • Kato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(11):1506–1517.
  • Keam SJ Toripalimab: first global approval. Drugs. 2019 Apr;79(5):573–578.
  • Markham A, Keam SJ Camrelizumab: first global approval. Drugs. 2019 Aug;79(12):1355–1361.
  • Hoy SM Sintilimab: first global approval. Drugs. 2019 Feb;79(3):341–346.
  • Huang J, Xu J, Chen Y, et al. Camrelizumab versus investigator’s choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2020 2020 May 13.
  • Xu J, Li Y, Fan Q, et al. Sintilimab in patients with advanced esophageal squamous cell carcinoma refractory to previous chemotherapy: A randomized, open-label phase II trial (ORIENT-2). 2020; ASCO Virtual Scientific Program: American Society of Clinical Oncology.
  • Wang F, Ren C, Zhao Q, et al. Association of frequent amplification of chromosome 11q13 in esophageal squamous cell cancer with clinical benefit to immune check point blockade. J clin oncol. 2019;37(15_suppl):4036.
  • Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med. 2018;378(22):2078–2092.
  • Bracci L, Schiavoni G, Sistigu A, et al. Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer. Cell Death Differ. 2014 Jan 01;21(1):15–25.
  • Wang Y-J, Fletcher R, Yu J, et al. Immunogenic effects of chemotherapy-induced tumor cell death. Genes Dis. 2018 Sep 01;5(3):194–203.
  • Zhang B, Qi L, Wang X, et al. Phase 2 study of camrelizumab (anti-PD-1 antibody) combined with apatinib and chemotherapy for the first-line treatment of advanced esophageal squamous cell carcinoma. 2019; ASCO Annual Meeting: American Society of Clinical Oncology, San Francisco, CA, USA.
  • Liao XY, Liu CY, He JF, et al. Combination of checkpoint inhibitors with radiotherapy in esophageal squamous cell carcinoma treatment: A novel strategy. Oncol Letters 2019 Nov;18(5):5011–5021.
  • Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015 Apr 1;520(7547):373–377.
  • Lim SH, Hong M, Ahn S, et al. Changes in tumour expression of programmed death-ligand 1 after neoadjuvant concurrent chemoradiotherapy in patients with squamous oesophageal cancer. Euro J Cancer (Oxford, England: 1990). 2016 Jan;52: 1–9.
  • Hong MH, Kim H, Park SY, et al. A phase II trial of preoperative chemoradiotherapy and pembrolizumab for locally advanced esophageal squamous cell carcinoma (ESCC). J clin oncol. 2019;37(15_suppl):4027.
  • Jing Z, Du D, Zhang N, et al. Combination of radiation therapy and anti-PD-1 antibody SHR-1210 in treating patients with esophageal squamous cell cancer. Int J Radiat Oncol Biol Phys. 2018;102(3):e31.
  • Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342–2350.
  • Goldberg MV, Drake CG LAG-3 in cancer immunotherapy. Curr Top Microbiol Immunol 2011;344:269–278.
  • Lui Y, Davis SJ LAG-3: a very singular immune checkpoint. Nat Immunol. 2018 Dec 1;19(12):1278–1279.
  • Long L, Zhang X, Chen F, et al. The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy. Genes Cancer. 2018 May;9(5–6):176–189.
  • Wang W, Chen D, Zhao Y, et al. Characterization of LAG-3, CTLA-4, and CD8(+) TIL density and their joint influence on the prognosis of patients with esophageal squamous cell carcinoma. Ann Transl Med. 2019 Dec;7(23):776.
  • Zhang Y, Liu YD, Luo YL, et al. Prognostic value of Lymphocyte Activation Gene-3 (LAG-3) expression in esophageal squamous cell carcinoma. J Cancer. 2018;9(22):4287–4293.
  • Labadie BW, Bao R, Luke JJ. Reimagining IDO pathway inhibition in cancer immunotherapy via downstream focus on the tryptophan-kynurenine-aryl hydrocarbon axis. Clin Cancer Res. 2019 Mar 1;25(5):1462–1471.
  • Cheong JE, Sun L. Targeting the IDO1/TDO2-KYN-AhR pathway for cancer immunotherapy - challenges and opportunities. Trends Pharmacol Sci. 2018 Mar;39(3):307–325.
  • Kiyozumi Y, Baba Y, Okadome K, et al. IDO1 expression is associated with immune tolerance and poor prognosis in patients with surgically resected esophageal cancer. Ann Surg. 2019 Jun;269(6):1101–1108.
  • Long GV, Dummer R, Hamid O, et al. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Lancet Oncol. 2019;20(8):1083–1097.
  • Iinuma H, Fukushima R, Inaba T, et al. Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients. J Transl Med 2014 Apr 3;12:84.
  • Katsuda M, Iwahashi M, Miyazawa M, et al. Therapeutic peptide vaccince therapy in combination with CpG-B for the patients with advanced esophageal squamous cell carcinoma. J clin oncol. 2016;34(15_suppl):e14585–e14585.
  • Mimura K, Yamada L, Ujiie D, et al. Immunotherapy for esophageal squamous cell carcinoma: a review. Fukushima J Med Sci. 2018 Aug 29;64(2):46–53.
  • Kono K, Iinuma H, Akutsu Y, et al. Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens. J Transl Med 2012 Jul 9;10:141.
  • Toh U, Yamana H, Sueyoshi S, et al. Locoregional cellular immunotherapy for patients with advanced esophageal cancer. Clin Cancer Res. 2000;6(12):4663–4673.
  • Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2018;380(1):45–56.
  • Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–2544.
  • Jochems C, Tritsch SR, Pellom ST, et al. Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824). Oncotarget. 2017 Sep 26;8(43):75217–75231.
  • Worthington JJ, Fenton TM, Czajkowska BI, et al. Regulation of TGFβ in the immune system: an emerging role for integrins and dendritic cells. Immunobiology. 2012 Dec;217(12):1259–1265.
  • Ungefroren H Blockade of TGF-β signaling: a potential target for cancer immunotherapy? Expert Opin Ther Targets. 2019 Aug 3;23(8):679–693.
  • Lin CC, Doi T, Muro K, et al. Phase I study results from an esophageal squamous cell carcinoma (ESCC) cohort treated with M7824 (MSB0011359C), a bifunctional fusion protein targeting transforming growth factor β (TGF-β) and PD-L1. Ann Oncol. 2018;29:viii215–viii216.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.