Recent advances in immune-based approaches for the treatment of esophagogastric cancer

References

• Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021 May;71(3):209–249.
   PubMed Web of Science ®Google Scholar
• Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948–1957.
   PubMed Web of Science ®Google Scholar
• Shapiro J, van Lanschot JJB, Hulshof M, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090–1098.
   PubMed Web of Science ®Google Scholar
• Powell J, McConkey CC. Increasing incidence of adenocarcinoma of the gastric cardia and adjacent sites. Br J Cancer. 1990 Sep;62(3):440–443.
   PubMed Web of Science ®Google Scholar
• Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer. 1998 Nov 15;83(10):2049–2053.
   PubMed Web of Science ®Google Scholar
• Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.
   PubMedGoogle Scholar
• Japanese Gastric Cancer Association, Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011 Jun;14(2):101–112.
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research Network, Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014 Sep 11;513(7517):202–209.
   PubMed Web of Science ®Google Scholar
• Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687–697.
   PubMed Web of Science ®Google Scholar
• Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020 Jun 18;382(25):2419–2430.
   PubMed Web of Science ®Google Scholar
• Wainberg ZA, Enzinger PC, Kang Y-K, et al. Randomized double-blind placebo-controlled phase 2 study of bemarituzumab combined with modified FOLFOX6 (mFOLFOX6) in first-line (1L) treatment of advanced gastric/gastroesophageal junction adenocarcinoma (FIGHT). J clin oncol. 2021;39(3_suppl): 160-160. DOI:https://doi.org/10.1200/JCO.2021.39.3_suppl.160.
   Google Scholar
• Sahin U, Türeci Ö, Manikhas G, et al. FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma. Ann Oncol. 2021 May;32(5):609–619.
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646–674.
   PubMed Web of Science ®Google Scholar
• Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–360.
   PubMed Web of Science ®Google Scholar
• Lee Y, Auh SL, Wang Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009 Jul 16;114(3):589–595.
   PubMed Web of Science ®Google Scholar
• The Cancer Genome Atlas Research Network, Integrated genomic characterization of oesophageal carcinoma. Nature. 2017 Jan 12;541(7636):169–175.
   PubMed Web of Science ®Google Scholar
• Ubukata H, Motohashi G, Tabuchi T, et al. Evaluations of interferon-γ/interleukin-4 ratio and neutrophil/lymphocyte ratio as prognostic indicators in gastric cancer patients. J Surg Oncol. 2010 Dec 1;102(7):742–747.
   PubMed Web of Science ®Google Scholar
• Chen JG, Xia JC, Liang XT, et al. Intratumoral expression of IL-17 and its prognostic role in gastric adenocarcinoma patients. Int J Biol Sci. 2011 Jan 11;7(1):53–60.
   PubMed Web of Science ®Google Scholar
• Fridman WH, Pagès F, Sautès-Fridman C, et al. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012 Mar 15;12(4):298–306.
   PubMed Web of Science ®Google Scholar
• Noma T, Makino T, Ohshima K, et al. Immunoscore signatures in surgical specimens and tumor-infiltrating lymphocytes in pretreatment biopsy predict treatment efficacy and survival in esophageal cancer. Ann Surg. 2021 Jul 29;Publish Ahead of Print. DOI:https://doi.org/10.1097/SLA.0000000000005104
   Google Scholar
• Mlecnik B, Bifulco C, Bindea G, et al. Multicenter international society for immunotherapy of cancer study of the consensus immunoscore for the prediction of survival and response to chemotherapy in stage III Colon cancer. J Clin Oncol. 2020 Nov 1;38(31):3638–3651.
   PubMed Web of Science ®Google Scholar
• Apetoh L, Ghiringhelli F, Tesniere A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007 Sep;13(9):1050–1059.
   PubMed Web of Science ®Google Scholar
• Yu Y, Ma X, Zhang Y, et al. Changes in expression of multiple checkpoint molecules and infiltration of tumor immune cells after neoadjuvant chemotherapy in gastric cancer. J Cancer. 2019;10(12):2754–2763.
   PubMed Web of Science ®Google Scholar
• Fukuoka E, Yamashita K, Tanaka T, et al. Neoadjuvant chemotherapy increases PD-L1 expression and CD8(+) tumor-infiltrating lymphocytes in esophageal squamous cell carcinoma. Anticancer Res. 2019 Aug;39(8):4539–4548.
   PubMed Web of Science ®Google Scholar
• Christina Svensson M, Lindén A, Nygaard J, et al. T cells, B cells, and PD-L1 expression in esophageal and gastric adenocarcinoma before and after neoadjuvant chemotherapy: relationship with histopathological response and survival. Oncoimmunology. 2021 May 20;10(1):1921443.
   PubMed Web of Science ®Google Scholar
• Kang C, Jeong SY, Song SY, et al. The emerging role of myeloid-derived suppressor cells in radiotherapy. Radiat Oncol J. 2020 Mar;38(1):1–10.
   PubMed Web of Science ®Google Scholar
• Sato H, Niimi A, Yasuhara T, et al. DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells. Nat Commun. 2017 Nov 24;8(1):1751.
   PubMed Web of Science ®Google Scholar
• Shevtsov M, Sato H, Multhoff G, et al. Novel approaches to improve the efficacy of immuno-radiotherapy. Front Oncol. 2019;9:156.
   PubMed Web of Science ®Google Scholar
• Kozin SV, Kamoun WS, Huang Y, et al. Recruitment of myeloid but not endothelial precursor cells facilitates tumor regrowth after local irradiation. Cancer Res. 2010 Jul 15;70(14):5679–5685.
   PubMed Web of Science ®Google Scholar
• Peng L, He W, Ye F, et al. Identification of tumor-infiltrating lymphocyte subpopulations correlated with patient prognosis in esophageal squamous cell carcinoma. J Int Med Res. 2021 May;49(5):3000605211016206.
   Web of Science ®Google Scholar
• Jiang Y, Awi L, Wong A, et al. Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma. Oncotarget. 2017 May 2;8(18):30175–30189.
   PubMedGoogle Scholar
• Taube JM, Anders RA, Young GD, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012 Mar 28;4(127):127ra37.
   PubMed Web of Science ®Google Scholar
• Thompson ED, Zahurak M, Murphy A, et al. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. 2017 May;66(5):794–801.
   PubMed Web of Science ®Google Scholar
• Liu T, Peng L, Yu P, et al. Increased circulating Th22 and Th17 cells are associated with tumor progression and patient survival in human gastric cancer. J Clin Immunol. 2012 Dec;32(6):1332–1339.
   PubMed Web of Science ®Google Scholar
• Wakatsuki K, Sho M, Yamato I, et al. Clinical impact of tumor-infiltrating CD45RO⁺ memory T cells on human gastric cancer. Oncol Rep. 2013 May;29(5):1756–1762.
   PubMed Web of Science ®Google Scholar
• Kulangara K, Zhang N, Corigliano E, et al. Clinical utility of the combined positive score for programmed death Ligand-1 expression and the approval of pembrolizumab for treatment of gastric cancer. Arch Pathol Lab Med. 2019 Mar;143(3):330–337.
   PubMed Web of Science ®Google Scholar
• Dolled-Filhart M, Locke D, Murphy T, et al. Development of a prototype immunohistochemistry assay to measure programmed death Ligand-1 expression in tumor tissue. Arch Pathol Lab Med. 2016 Nov;140(11):1259–1266.
   PubMed Web of Science ®Google Scholar
• Ostrand-Rosenberg S, Horn LA, Ciavattone NG. Radiotherapy both promotes and inhibits myeloid-derived suppressor cell function: novel strategies for preventing the tumor-protective effects of radiotherapy. Front Oncol. 2019;9:215.
   PubMed Web of Science ®Google Scholar
• Muro K, Chung HC, Shankaran V, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016 Jun;17(6):717–726.
   PubMed Web of Science ®Google Scholar
• Doi T, Piha-Paul SA, Jalal SI, et al. Safety and antitumor activity of the anti-programmed death-1 antibody pembrolizumab in patients with advanced esophageal carcinoma. J Clin Oncol. 2018 Jan 1;36(1):61–67.
   PubMed Web of Science ®Google Scholar
• Fuchs CS, Doi T, Jang RW, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction Cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018 May 10;4(5):e180013.
   PubMed Web of Science ®Google Scholar
• Kang YK, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461–2471.
   PubMed Web of Science ®Google Scholar
• Curran MA, Montalvo W, Yagita H, et al. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4275–4280.
   PubMed Web of Science ®Google Scholar
• Selby MJ, Engelhardt JJ, Johnston RJ, et al. Preclinical development of ipilimumab and nivolumab combination immunotherapy: mouse tumor models, in vitro functional studies, and cynomolgus macaque toxicology. PLoS One. 2016;11(9):e0161779.
   PubMed Web of Science ®Google Scholar
• Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015 Jul 2;373(1):23–34.
   PubMed Web of Science ®Google Scholar
• Escudier B, Motzer RJ, Tannir NM, et al. Efficacy of nivolumab plus ipilimumab according to number of IMDC risk factors in checkmate 214. Eur Urol. 2020 Apr;77(4):449–453.
   PubMed Web of Science ®Google Scholar
• Janjigian YY, Bendell J, Calvo E, et al. CheckMate-032 study: efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer. J Clin Oncol. 2018 Oct 1;36(28):2836–2844.
   PubMed Web of Science ®Google Scholar
• Pietrantonio F, Randon G, Di Bartolomeo M, et al. Predictive role of microsatellite instability for PD-1 blockade in patients with advanced gastric cancer: a meta-analysis of randomized clinical trials. ESMO Open. 2021 Feb;6(1):100036.
   PubMed Web of Science ®Google Scholar
• Kelly RJ, Lee J, Bang YJ, et al. Safety and efficacy of durvalumab and tremelimumab alone or in combination in patients with advanced gastric and gastroesophageal junction adenocarcinoma. Clin Cancer Res. 2020 Feb 15;26(4):846–854.
   PubMed Web of Science ®Google Scholar
• Kojima T, Shah MA, Muro K, et al. Randomized phase III KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer. J Clin Oncol. 2020 Dec 10;38(35):4138–4148.
   PubMed Web of Science ®Google Scholar
• Kato K, Sun JM, Shah MA, et al. Pembrolizumab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced esophageal cancer: the phase 3 KEYNOTE-590 study. Ann Oncol. 2020;31:S1192–S1193.
   Web of Science ®Google Scholar
• Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27–40.
   PubMed Web of Science ®Google Scholar
• Boku N, Ryu MH, Kato K, et al. Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4). Ann Oncol. 2019 Feb 1;30(2):250–258.
   PubMed Web of Science ®Google Scholar
• Janjigian YY, Ajani JA, Moehler M, et al. LBA7 - Nivolumab (NIVO) plus chemotherapy (Chemo) or ipilimumab (IPI) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): checkMate 649 study. Ann Oncol. 2021;32:S1283–S1346.
   Web of Science ®Google Scholar
• Xu J, Jiang H, Pan Y, et al. LBA53 - Sintilimab plus chemotherapy (chemo) versus chemo as first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (ORIENT-16): first results of a randomized, double-blind, phase III study. Ann Oncol. 2021;32:S1283–S1346.
   Google Scholar
• Janjigian YY, Maron SB, Chatila WK, et al. First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2020 Jun;21(6):821–831.
   PubMed Web of Science ®Google Scholar
• Chung HC, Bang YJ, Sf C, et al. First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. Future Oncol. 2021 Feb;17(5):491–501.
   PubMed Web of Science ®Google Scholar
• Janjigian YY, Kawazoe A, Yanez PE, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (G/GEJ) cancer: initial findings of the global phase 3 KEYNOTE-811 study. J clin oncol. 2021;39(15_suppl): 4013-4013. DOI:https://doi.org/10.1200/JCO.2021.39.15_suppl.4013.
   Google Scholar
• R-h X, Luo H, Lu J, et al. ESCORT-1st: a randomized, double-blind, placebo-controlled, phase 3 trial of camrelizumab plus chemotherapy versus chemotherapy in patients with untreated advanced or metastatic esophageal squamous cell carcinoma (ESCC). J clin oncol. 2021;39(15_suppl): 4000-4000. DOI:https://doi.org/10.1200/JCO.2021.39.15_suppl.4000.
   Google Scholar
• Shen L, Lu ZH, Wang JY, et al. LBA52 - Sintilimab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced or metastatic esophageal squamous cell cancer: first results of the phase III ORIENT-15 study. Ann Oncol. 2021;32:S1283–S1346.
   Web of Science ®Google Scholar
• Xu R, Wang F, Cui C. 1373MO - Jupiter-06: a randomized, double-blind, phase III study of toripalimab versus placebo in combination with first-line chemotherapy for treatment naive advanced or metastatic esophageal squamous cell carcinoma (ESCC). Ann Oncol. 2021;32:S1040–S1075.
   Web of Science ®Google Scholar
• 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 Nov;20(11):1506–1517.
   PubMed Web of Science ®Google Scholar
• Shen L, Kato K, Kim S-B, et al. RATIONALE 302: randomized, phase 3 study of tislelizumab versus chemotherapy as second-line treatment for advanced unresectable/metastatic esophageal squamous cell carcinoma. J clin oncol. 2021;39(15_suppl): 4012-4012. DOI:https://doi.org/10.1200/JCO.2021.39.15_suppl.4012.
   Google Scholar
• Feeney K, Kelly R, Lipton LR, et al. CA224-060: a randomized, open label, phase II trial of relatlimab (anti-LAG-3) and nivolumab with chemotherapy versus nivolumab with chemotherapy as first-line treatment in patients with gastric or gastroesophageal junction adenocarcinoma. J clin oncol. 2019;37(15_suppl): TPS4143–TPS4143.
   Google Scholar
• Curigliano G, Gelderblom H, Mach N, et al. Phase I/Ib clinical trial of sabatolimab, an anti-TIM-3 antibody, alone and in combination with spartalizumab, an anti-PD-1 antibody, in advanced solid tumors. Clin Cancer Res. 2021 Jul 1;27(13):3620–3629.
   PubMed Web of Science ®Google Scholar
• Aanur P, Gutierrez M, Kelly RJ, et al. Fraction (fast real-time assessment of combination therapies in immuno-oncology)-gastric cancer (GC): a randomized, open-label, adaptive, phase 2 study of nivolumab in combination with other immuno-oncology (IO) agents in patients with advanced GC. J clin oncol. 2017;35(15_suppl): TPS4137–TPS4137.
   Google Scholar
• Oh D-Y, Ajani JA, Bang Y-J, et al. Phase Ib/II open-label, randomized evaluation of 2L atezolizumab (atezo) + BL-8040 versus control in MORPHEUS-pancreatic ductal adenocarcinoma (M-PDAC) and MORPHEUS-gastric cancer (M-GC). J clin oncol. 2020;38(4_suppl): 712-712. DOI:https://doi.org/10.1200/JCO.2020.38.4_suppl.712.
   Google Scholar
• Tabernero J, Cohen D, Van Cutsem E, et al. P-154 A randomized phase 3 study evaluating the efficacy and safety of first-line pembrolizumab plus lenvatinib plus chemotherapy compared with chemotherapy in patients with advanced/metastatic gastroesophageal adenocarcinoma: LEAP-015. Ann Oncol. 2021 July 1;32:S151–S152.
   Google Scholar
• Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021 Apr 1;384(13):1191–1203.
   PubMed Web of Science ®Google Scholar
• Moehler M, Ajani JA, Kuzdzal J, et al. 1381P - Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): 14-month follow-up of CheckMate 577. Ann Oncol. 2021;32:S1040–S1075.
   Web of Science ®Google Scholar
• Smyth E, Knödler M, Giraut A, et al. VESTIGE: adjuvant immunotherapy in patients with resected esophageal, gastroesophageal junction and gastric cancer following preoperative chemotherapy with high risk for recurrence (N+ and/or R1): an open label randomized controlled phase-2-study. Front Oncol. 2019;9:1320.
   PubMed Web of Science ®Google Scholar
• Bang YJ, Van Cutsem E, Fuchs CS, et al. KEYNOTE-585: phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer. Future Oncol. 2019 Mar;15(9):943–952.
   PubMed Web of Science ®Google Scholar
• Kato K, Shah MA, Enzinger P, et al. KEYNOTE-590: phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. Future Oncol. 2019 Apr;15(10):1057–1066.
   PubMed Web of Science ®Google Scholar
• Shitara K, Van Cutsem E, Bang YJ, et al. Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line, advanced gastric cancer: the KEYNOTE-062 phase 3 randomized clinical trial. JAMA Oncol. 2020 Oct 1;6(10):1571–1580.
   PubMed Web of Science ®Google Scholar
• Bang YJ, Kang YK, Catenacci DV, et al. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer. 2019 Jul;22(4):828–837.
   PubMed Web of Science ®Google Scholar
• Moehler M, Dvorkin M, Boku N, et al. Phase III trial of avelumab maintenance after first-line induction chemotherapy versus continuation of chemotherapy in patients with gastric cancers: results from JAVELIN gastric 100. J Clin Oncol. 2021 Mar 20;39(9):966–977.
   PubMed Web of Science ®Google Scholar
• Shitara K, Özgüroğlu M, Bang YJ, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123–133.
   PubMed Web of Science ®Google Scholar
• Chen LT, Satoh T, Ryu MH, et al. A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data. Gastric Cancer. 2020 May;23(3):510–519.
   PubMed Web of Science ®Google Scholar
• 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 Apr 1;5(4):546–550.
   PubMed Web of Science ®Google Scholar
• Bang YJ, Ruiz EY, Van Cutsem E, et al. Phase III, randomised trial of avelumab versus physician’s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052–2060.
   PubMed Web of Science ®Google Scholar