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Review

Emerging biological drugs for the treatment of gastroesophageal adenocarcinoma

, &
Pages 385-400 | Received 25 Jun 2021, Accepted 22 Nov 2021, Published online: 28 Nov 2021

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;71:209–249.
  • THUN MJ, WILD CP, and COLDITZ, G. Framework for understanding cancer prevention. Cerhan JR En Schottenfeld and Fraumeni Cancer Epidemiology and Prevention. Fourth ed. New York (NY): Oxford University Press; 2017. pp. 1193-1204 .
  • Smyth E, Verheij M, Allum W, et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27:v38–v49.
  • Network CGAR. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–209.
  • Pietrantonio F, Miceli R, and Raimondi A, et al. Individual patient data meta-analysis of the value of microsatellite instability as a biomarker in gastric cancer J Clin Oncol . 2019;37(35):3392–3400 .
  • Sohn BH, Hwang J-E, Jang H-J, et al. Clinical significance of four molecular subtypes of gastric cancer identified by the cancer genome atlas project. Clin Cancer Res. 2017;23:4441–4449.
  • Janjigian YY, Sanchez-Vega F, Jonsson P, et al. Genetic predictors of response to systemic therapy in esophagogastric cancer. Cancer Discov. 2018;8:49–58.
  • Cristescu R, Lee J, Nebozhyn M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21:449–456.
  • Feng RM, Zong YN, Cao SM, et al. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics? Cancer Commun. 2019;39:1–12.
  • Tabernero J, Hoff PM, Shen L, et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018;19:1372–1384.
  • Satoh T, Xu R-H, Chung HC, et al. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: tyTAN—a randomized, phase III study. J Clin Oncol. 2014;53:6136.
  • Hecht JR, Bang Y-J, and Qin S, et al. Lapatinib in combination with capecitabine plus oxaliplatin (CapeOx) in HER2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma (AC): the TRIO-013/LOGiC trial. J Clin Oncol. 2013;(suppl; abstr LBA4001). doi:https://doi.org/10.1200/jco.2013.31.18_suppl.lba4001
  • Thuss-Patience PC, Shah MA, Ohtsu A, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017;18:640–653.
  • Waddell T, Chau I, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3) a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:481–489.
  • Lordick F, Kang YK, Chung HC, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:490–499.
  • 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;15:894–904.
  • Catenacci DV, Tebbutt NC, Davidenko I, et al. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:1467–1482.
  • Shah MA, Bang Y-J, and Lordick F, et al. Effect of fluorouracil, leucovorin, and oxaliplatin with or without onartuzumab in HER2-negative, MET-positive gastroesophageal adenocarcinoma: the METGastric randomized clinical trial. JAMA Oncol. 2017;3(5): 620–627 .
  • Alsina M, Gullo I, and Carneiro F Intratumoral heterogeneity in gastric cancer: anew challenge to face. Annals of Oncology. 2017;28(5): 912–913 .
  • Nakamura Y, Kawazoe A, and Lordick F, et al. Biomarker-targeted therapies for advanced-stage gastric and gastro-oesophageal junction cancers: an emerging paradigm. Nat Rev Clin Oncol. 2021;18(8):473–487.
  • Pectasides E, Stachler MD, Derks S, et al. Genomic heterogeneity as a barrier to precision medicine in gastroesophageal adenocarcinoma. Cancer Discov. 2018;8:37–48.
  • Nakamura Y, Sasaki A, and Yukami H, et al. Emergence of concurrent multiple EGFR mutations and MET amplification in a patient with EGFR-amplified advanced gastric cancer treated with cetuximab. JCO Precis Oncol. 2020;4:1407–1413. DOI:https://doi.org/10.1200/PO.20.00263.
  • Parikh AR, Leshchiner I, Elagina L, et al. Liquid versus tissue biopsy for detecting acquired resistance and tumor heterogeneity in gastrointestinal cancers. Nat Med. 2019;25:1415–1421.
  • American Cancer Society. Facts & Figures 2021. Atlanta: American Cancer Society; 2021.
  • Smyth EC, Nilsson M, Grabsch HI, et al. Gastric cancer. Lancet. 2020;396:635–648.
  • Muro K, Van Cutsem E, Narita Y, et al. Pan-Asian adapted ESMO clinical practice guidelines for the management of patients with metastatic gastric cancer: a JSMO–ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS. Ann Oncol. 2019;30:19–33.
  • Wang F-H, Shen L, Li J, et al. The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer. Cancer Commun. 2019;39:1–31.
  • Bang Y-J, 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;376:687–697.
  • Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–1235.
  • Shitara K, Doi T, Dvorkin M, et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19:1437–1448.
  • Kang Y-K, 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;390:2461–2471.
  • 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;4:e180013–e.
  • Janjigian YY, Shitara K, and 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 398(10294): 27–40 .
  • Kato K, Shah M, Enzinger P, et al. Phase III KEYNOTE-590 study of chemotherapy+ pembrolizumab versus chemotherapy+ placebo as first-line therapy for patients (Pts) with advanced esophageal or esophagogastric junction (E/EGJ) cancer. Ann Oncol. 2018;29:viii268–viii9.
  • Chao J, Fuchs CS, and Shitara K, et al. Assessment of pembrolizumab therapy for the treatment of microsatellite instability–high gastric or gastroesophageal junction cancer among patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 clinical trials. JAMA Oncol. 2021;7(6): 895–902 .
  • Kim W-H, Gomez-Izquierdo L, Vilardell F, et al. HER2 status in gastric and gastroesophageal junction cancer: results of the large, multinational HER-EAGLE study. Appl Immunohistochem Mol Morphol. 2018;26:239–245.
  • Tabernero J, Hoff P, Shen L, et al. 1423MO End-of-study analysis from JACOB: a phase III study of pertuzumab (P)+ trastuzumab (H) and chemotherapy (CT) in HER2-positive metastatic gastric or gastro-esophageal junction cancer (mGC/GEJC). Ann Oncol. 2020;31:S900–S1.
  • Ruschoff J, Dietel M, Baretton G, et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010;457:299–307.
  • Shah MA, Kang Y-K, Thuss-Patience PC, et al. Biomarker analysis of the GATSBY study of trastuzumab emtansine versus a taxane in previously treated HER2-positive advanced gastric/gastroesophageal junction cancer. Gastric Cancer. 2019;22:803–816.
  • Kim J, Fox C, and Peng S, et al. Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma J Clin Invest. 2014;124:5145–5158.
  • Shitara K, Bang Y-J, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020;382:2419–2430.
  • 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;21:821–831.
  • 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. Wolters Kluwer Health; 2021.
  • Nagatsuma AK, Aizawa M, Kuwata T, et al. Expression profiles of HER2, EGFR, MET and FGFR2 in a large cohort of patients with gastric adenocarcinoma. Gastric Cancer. 2015;18:227–238.
  • Lordick F, Kang Y-K, Salman P, et al. Clinical outcome according to tumor HER2 status and EGFR expression in advanced gastric cancer patients from the EXPAND study. American Society of Clinical Oncology; 2013.
  • Petty RD, Dahle-Smith A, and Stevenson DA, et al. Gefitinib and epidermal growth factor receptor gene copy number aberrations in esophageal cancer. J Clin Oncol. 2017;35(20):2279–2287.
  • Janjigian YY, Tang LH, Coit DG, et al. MET expression and amplification in patients with localized gastric cancer. Cancer Epidemiol Prev Biomarkers. 2011;20:1021–1027.
  • Lee H, Kim M, Lee H, et al. MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome. Br J Cancer. 2012;107:325–333.
  • Ohtsu A, Shah MA, Van Cutsem E, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29:3968–3976.
  • Fuchs CS, Shitara K, Di Bartolomeo M, et al. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20:420–435.
  • Li J, Qin S, Xu J, et al. Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2016;34:1448–1454.
  • Kang Y-K, Kang W, Di Bartolomeo M, et al. Randomized phase III ANGEL study of rivoceranib (apatinib)+ best supportive care (BSC) vs placebo+ BSC in patients with advanced/metastatic gastric cancer who failed≥ 2 prior chemotherapy regimens. Ann Oncol. 2019;30:v877–v8.
  • Van Cutsem E, de Haas S, Kang Y-K, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol. 2012;30:2119–2127.
  • Sahasrabudhe R, Lott P, Bohorquez M, et al. Germline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancer. Gastroenterology. 2017;152(983–6):e6.
  • Bang Y-J, Xu R-H, Chin K, et al. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:1637–1651.
  • Shitara K, Özgüroğlu M, Bang Y-J, 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;392:123–133.
  • Shitara K, Van Cutsem E, Bang Y-J, 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;6:1571–1580.
  • Shitara K, Özgüroğlu M, Bang Y-J, et al. The association of tissue tumor mutational burden (tTMB) using the Foundation Medicine genomic platform with efficacy of pembrolizumab versus paclitaxel in patients (pts) with gastric cancer (GC) from KEYNOTE-061. American Society of Clinical Oncology; 2020.
  • Fuchs CS, Özgüroğlu M, Bang Y-J, et al. The association of molecular biomarkers with efficacy of pembrolizumab versus paclitaxel in patients with gastric cancer (GC) from KEYNOTE-061. American Society of Clinical Oncology; 2020.
  • Wyrwicz L, Lee K, Van Cutsem E, et al. 1442P association of TMB using the Foundation Medicine Companion Diagnostic (F1CDx) with efficacy of first-line pembrolizumab (pembro) or pembro plus chemotherapy (pembro+ chemo) versus chemo in patients with gastric cancer (gc) from KEYNOTE-062. Ann Oncol. 2020;31:S907–S8.
  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–264.
  • Catenacci DV, Moya S, Lomnicki S, et al. Personalized antibodies for gastroesophageal adenocarcinoma (PANGEA): a phase II study evaluating an individualized treatment strategy for metastatic disease. Cancer Discov. 2021;11:308–325.
  • Lee J, Kim ST, Kim K, et al. Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: the VIKTORY umbrella trial. Cancer Discov. 2019;9:1388–1405.
  • Yuki S, Shitara K, Kadowaki S, et al. The nationwide cancer genome screening project in Japan SCRUM-Japan GI-SCREEN: efficient identification of cancer genome alterations in advanced gastric cancer (GC). American Society of Clinical Oncology; 2018.
  • Nakamura Y, Taniguchi H, Ikeda M, et al. Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies. Nat Med. 2020;26:1859–1864.
  • 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. 2017;74:9846.
  • Yamaguchi K, Bang Y, Iwasa S, et al. 1422MO Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-low, advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: results of the exploratory cohorts in the phase II, multicenter, open-label DESTINY-Gastric01 study. Ann Oncol. 2020;31:S899–S900.
  • Catenacci DV, Kang Y-K, Park H, et al. Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22–05): a single-arm, phase 1b–2 trial. Lancet Oncol. 2020;21:1066–1076.
  • Kulukian A, Lee P, Taylor J, et al. Preclinical activity of HER2-selective tyrosine kinase inhibitor tucatinib as a single agent or in combination with trastuzumab or docetaxel in solid tumor models. Mol Cancer Ther. 2020;19:976–987.
  • Meric-Bernstam F, Hamilton EP, Beeram M, et al. Zanidatamab (ZW25) in HER2-expressing gastroesophageal adenocarcinoma (GEA): results from a phase I study. American Society of Clinical Oncology; 2021.
  • Al-Batran S, Haag G, Ettrich T, et al. 1421MO Final results and subgroup analysis of the PETRARCA randomized phase II AIO trial: perioperative trastuzumab and pertuzumab in combination with FLOT versus FLOT alone for HER2 positive resectable esophagogastric adenocarcinoma. Ann Oncol. 2020;31:S899.
  • Rivera F, Izquierdo-Manuel M, García-Alfonso P, et al. Perioperative trastuzumab, capecitabine and oxaliplatin in patients with HER2-positive resectable gastric or gastro-oesophageal junction adenocarcinoma: NEOHX phase II trial. Eur J Cancer. 2021;145:158–167.
  • Davies A, Myoteri D, Zylstra J, et al. Lymph node regression and survival following neoadjuvant chemotherapy in oesophageal adenocarcinoma. Br J Surg. 2018;105:1639–1649.
  • Reynolds JV, Preston SR, O’Neill B, et al. Neo-AEGIS (Neoadjuvant trial in adenocarcinoma of the esophagus and esophago-gastric junction international study): preliminary results of phase III RCT of CROSS versus perioperative chemotherapy (Modified MAGIC or FLOT protocol). (NCT01726452). Wolters Kluwer Health; 2021.
  • Wagner AD, Grabsch HI, Mauer M, et al. EORTC-1203-GITCG-the “INNOVATION”-trial: effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab plus pertuzumab, in the perioperative treatment of HER2 positive, gastric and gastroesophageal junction adenocarcinoma on pathologic response rate: a randomized phase II-intergroup trial of the EORTC-Gastrointestinal Tract Cancer Group, Korean Cancer Study Group and Dutch Upper GI-Cancer group. BMC Cancer. 2019;19:1–9.
  • Pearson A, Smyth E, Babina IS, et al. High-level clonal FGFR amplification and response to FGFR inhibition in a translational clinical trial. Cancer Discov. 2016;6:838–851.
  • Jang J, Kim HK, Bang H, et al. Antitumor effect of AZD4547 in a fibroblast growth factor receptor 2–Amplified gastric Cancer patient–Derived cell model. Transl Oncol. 2017;10:469–475.
  • Van Cutsem E, Bang Y-J, Mansoor W, et al. A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification Ann Oncol. 2015;28(6):1316–1324.
  • Goyal L, Shi L, Liu LY, et al. TAS-120 overcomes resistance to ATP-competitive FGFR inhibitors in patients with FGFR2 fusion–positive intrahepatic cholangiocarcinoma. Cancer Discov. 2019;9:1064–1079.
  • Bahleda R, Meric-Bernstam F, Goyal L, et al. Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1–4 inhibitor in patients with advanced solid tumors. Ann Oncol. 2020;31:1405–1412.
  • Catenacci DV, Rasco D, Lee J, et al. Phase I escalation and expansion study of bemarituzumab (FPA144) in patients with advanced solid tumors and FGFR2b-selected gastroesophageal adenocarcinoma. J Clin Oncol. 2020;38:2418.
  • 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). American Society of Clinical Oncology; 2021.
  • Liu JF, Barry WT, Birrer M, et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014;15:1207–1214.
  • Sahin U, Koslowski M, Dhaene K, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res. 2008;14:7624–7634.
  • Nakayama I, Shinozaki E, Sakata S, et al. Enrichment of CLDN18‐ARHGAP fusion gene in gastric cancers in young adults. Cancer Sci. 2019;110:1352–1363.
  • 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;32:609–619.
  • Zhan X, Wang B, Li Z, et al. Phase I trial of Claudin 18.2-specific chimeric antigen receptor T cells for advanced gastric and pancreatic adenocarcinoma. American Society of Clinical Oncology; 2019.
  • Russo GL, Moro M, Sommariva M, et al. Antibody–Fc/FcR interaction on macrophages as a mechanism for hyperprogressive disease in non–small cell lung cancer subsequent to PD-1/PD-L1 blockade. Clin Cancer Res. 2019;25:989–999.
  • Kamada T, Togashi Y, Tay C, et al. PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc Nat Acad Sci. 2019;116:9999–10008.
  • Fukuoka S, Hara H, Takahashi N, et al. Regorafenib plus nivolumab in patients with advanced gastric or colorectal cancer: an open-label, dose-escalation, and dose-expansion phase Ib trial (REGONIVO, EPOC1603). J Clin Oncol. 2020;38:2053–2061.
  • Kawazoe A, Fukuoka S, Nakamura Y, et al. Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. Lancet Oncol. 2020;21:1057–1065.
  • Liu Y, Han G, Li H, et al. Camrelizumab combined with FOLFOX as neoadjuvant therapy for resectable locally advanced gastric and gastroesophageal junction adenocarcinoma. American Society of Clinical Oncology; 2020.
  • Li H, Deng J, Ge S, et al. Phase II study of perioperative toripalimab in combination with FLOT in patients with locally advanced resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma. Wolters Kluwer Health; 2021.
  • Alcindor T, Opu T, Elkrief A, et al. Phase II trial of perioperative chemotherapy+ avelumab in locally advanced gastroesophageal adenocarcinoma: preliminary results. Wolters Kluwer Health; 2021.
  • Alsina M, Ponz-Sarvise M, Lopez Garcia D, et al. MONEO: a phase II study of avelumab (Av) plus FLOT in the peri-operative treatment for patients (pts) with resectable gastric or gastroesophageal junction cancer (GC). Wolters Kluwer Health; 2021.
  • Bang Y-J, 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;15:943–952.
  • Janjigian YY, Van Cutsem E, Muro K, et al. MATTERHORN: efficacy and safety of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer—A randomized, double-blind, placebo-controlled, phase 3 study. Wolters Kluwer Health; 2021.
  • 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. 2020;9:1320.
  • Deng N, Goh LK, Wang H, et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut. 2012;61:673–684.
  • Wagner AD, Unverzagt S, and Grothe W, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2010;(3):CD004064.
  • Kato K, Sun J, Shah M, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet . 2021;398(10302):759–771 .
  • Alsina M, Miquel JM, Diez M, et al. How I treat gastric adenocarcinoma. ESMO Open. 2019;4:e000521.

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