Skip to main content

Advertisement

Log in

Targeted Therapies in Advanced Gastric Cancer

  • Upper Gastrointestinal Cancers (JD Berlin, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Despite a decreasing incidence in the USA, gastric cancer is highly prevalent worldwide. Furthermore, gastric cancer remains highly lethal with median survival of less than 1 year for metastatic disease. The backbone of therapy against metastatic gastric cancer remains cytotoxic chemotherapy, but recent advances in the molecular understanding of gastric cancer have renewed hope within that targeted agents can be leveraged to improve survival and reduce toxicity. For example, in patients with human epidermal growth factor-2 (HER2)-positive gastric cancer, the addition of trastuzumab to frontline chemotherapy improves survival. In the second line, oncologists can now administer a vascular endothelial growth factor (VEGF) receptor inhibitor, ramucirumab, as a single agent or in combination with chemotherapy, and the immune checkpoint inhibitor pembrolizumab is approved in multiple settings dependent on the Programmed Death Ligand 1 (PD-L1) status. For patients with metastatic disease, our approach to standard of care in the first-line setting is a 5FU/platinum doublet with trastuzumab for HER2-positive tumors. In the second-line setting, most patients receive ramucirumab + paclitaxel, but those that are MSI high receive pembrolizumab. For squamous cell carcinoma of the esophagus with high PD-L1 status (combined positive score (CPS) ≥ 10), we recommend pembrolizumab in the second line. While for PD-L1 ≥ 1% gastroesophageal adenocarcinoma, we do not recommend pembrolizumab before the third-line setting, although this may change in the near future for CPS ≥ 10. The future landscape for targeted therapy in gastric cancer is promising. Numerous clinical trials evaluating the combination immune therapy with molecularly targeted agents are generating much excitement. Moreover, genomic data from The Cancer Center Genome (TCGA) and Asian Cancer Research Group (ACRG) classifications is being used to identify molecular subtypes to enable future clinical trials to include biomarker-enriched patient populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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.

    PubMed  Google Scholar 

  2. Rahman R, Asombang AW, Ibdah JA. Characteristics of gastric cancer in Asia. World J Gastroenterol. 2014;20(16):4483–90.

    PubMed  PubMed Central  Google Scholar 

  3. 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.

    CAS  PubMed  Google Scholar 

  4. Group G, Oba K, Paoletti X, Bang YJ, Bleiberg H, Burzykowski T, et al. Role of chemotherapy for advanced/recurrent gastric cancer: an individual-patient-data meta-analysis. Eur J Cancer. 2013;49(7):1565–77.

    Google Scholar 

  5. Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9.

    Google Scholar 

  6. Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21(5):449–56.

    CAS  PubMed  Google Scholar 

  7. Chivu-Economescu M, Matei L, Necula LG, Dragu DL, Bleotu C, Diaconu CC. New therapeutic options opened by the molecular classification of gastric cancer. World J Gastroenterol. 2018;24(18):1942–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Menard S, Pupa SM, Campiglio M, Tagliabue E. Biologic and therapeutic role of HER2 in cancer. Oncogene. 2003;22(42):6570–8.

    CAS  PubMed  Google Scholar 

  9. Gassmann M, Casagranda F, Orioli D, Simon H, Lai C, Klein R, et al. Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature. 1995;378(6555):390–4.

    CAS  PubMed  Google Scholar 

  10. Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science. 1986;232(4758):1644–6.

    CAS  PubMed  Google Scholar 

  11. Grillo F, Fassan M, Sarocchi F, Fiocca R, Mastracci L. HER2 heterogeneity in gastric/gastroesophageal cancers: from benchside to practice. World J Gastroenterol. 2016;22(26):5879–87.

    PubMed  PubMed Central  Google Scholar 

  12. Abrahao-Machado LF, Scapulatempo-Neto C. HER2 testing in gastric cancer: an update. World J Gastroenterol. 2016;22(19):4619–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Ruschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25(5):637–50.

    PubMed  Google Scholar 

  14. Bartley AN, Washington MK, Colasacco C, Ventura CB, Ismaila N, Benson AB 3rd, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35(4):446–64.

    CAS  PubMed  Google Scholar 

  15. Fujimoto-Ouchi K, Sekiguchi F, Yasuno H, Moriya Y, Mori K, Tanaka Y. Antitumor activity of trastuzumab in combination with chemotherapy in human gastric cancer xenograft models. Cancer Chemother Pharmacol. 2007;59(6):795–805.

    CAS  PubMed  Google Scholar 

  16. • Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki 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(9742):687–97 This study resulted in the FDA approval of the first HER2 directed therapy in gastric cancer.

    CAS  PubMed  Google Scholar 

  17. Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008;68(22):9280–90.

    CAS  PubMed  Google Scholar 

  18. Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, 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(5):640–53.

    CAS  PubMed  Google Scholar 

  19. Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009;9(7):463–75.

    CAS  PubMed  Google Scholar 

  20. Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 2009;69(24):9330–6.

    CAS  PubMed  Google Scholar 

  21. Kang YK, Rha SY, Tassone P, Barriuso J, Yu R, Szado T, et al. A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. Br J Cancer. 2014;111(4):660–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, 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(10):1372–84.

    CAS  PubMed  Google Scholar 

  23. Konecny GE, Pegram MD, Venkatesan N, Finn R, Yang G, Rahmeh M, et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res. 2006;66(3):1630–9.

    CAS  PubMed  Google Scholar 

  24. Iqbal S, Goldman B, Fenoglio-Preiser CM, Lenz HJ, Zhang W, Danenberg KD, et al. Southwest oncology group study S0413: a phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer. Ann Oncol. 2011;22(12):2610–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, et al. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC--a randomized phase III trial. J Clin Oncol. 2016;34(5):443–51.

    CAS  PubMed  Google Scholar 

  26. Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, 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;32(19):2039–49.

    CAS  PubMed  Google Scholar 

  27. Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol. 2019;20(6):827–36.

    CAS  PubMed  Google Scholar 

  28. Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, et al. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017;18(11):1512–22.

    CAS  PubMed  Google Scholar 

  29. Nordstrom JL, Gorlatov S, Zhang W, Yang Y, Huang L, Burke S, et al. Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcgamma receptor binding properties. Breast Cancer Res. 2011;13(6):R123.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Bang YJ, Giaccone G, Im SA, Oh DY, Bauer TM, Nordstrom JL, et al. First-in-human phase 1 study of margetuximab (MGAH22), an fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. Ann Oncol. 2017;28(4):855–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Catenacci DVT, Park H, Lockhart AC, Gold PJ, Enzinger PC, Nordstrom JL, et al. Phase 1b/2 study of margetuximab (M) plus pembrolizumab (P) in advanced HER2+ gastroesophageal junction (GEJ) or gastric (G) adenocarcinoma (GEA). J Clin Oncol. 2018;36(4_suppl):140.

    Google Scholar 

  32. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2(2):127–37.

    CAS  PubMed  Google Scholar 

  33. Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, 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(6):490–9.

    CAS  PubMed  Google Scholar 

  34. Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, 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(6):481–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Maron SB, Alpert L, Kwak HA, Lomnicki S, Chase L, Xu D, et al. Targeted therapies for targeted populations: anti-EGFR treatment for EGFR-amplified gastroesophageal adenocarcinoma. Cancer Discov. 2018;8(6):696–713.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Xu W, Yang Z, Lu N. Molecular targeted therapy for the treatment of gastric cancer. J Exp Clin Cancer Res. 2016;35:1.

    PubMed  PubMed Central  Google Scholar 

  37. Grigore D, Simionescu CE, Stepan A, Margaritescu C, Balasoiu M, Georgescu CC, et al. Assessment of CD105, alpha-SMA and VEGF expression in gastric carcinomas. Romanian J Morphol Embryol. 2013;54(3 Suppl):701–7.

    Google Scholar 

  38. Juttner S, Wissmann C, Jons T, Vieth M, Hertel J, Gretschel S, et al. Vascular endothelial growth factor-D and its receptor VEGFR-3: two novel independent prognostic markers in gastric adenocarcinoma. J Clin Oncol. 2006;24(2):228–40.

    PubMed  Google Scholar 

  39. Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 2005;65(3):671–80.

    CAS  PubMed  Google Scholar 

  40. Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, 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(30):3968–76.

    CAS  PubMed  Google Scholar 

  41. Shen L, Li J, Xu J, Pan H, Dai G, Qin S, et al. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer. 2015;18(1):168–76.

    CAS  PubMed  Google Scholar 

  42. Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31–9.

    CAS  PubMed  Google Scholar 

  43. • Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, 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(11):1224–35 This study resulted in the FDA approval of the first VEGF directed therapy in gastric cancer.

    CAS  PubMed  Google Scholar 

  44. Yoon HH, Bendell JC, Braiteh FS, Firdaus I, Philip PA, Cohn AL, et al. Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter phase II trial. Ann Oncol. 2016;27(12):2196–203.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, 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(3):420–35.

    CAS  PubMed  Google Scholar 

  46. Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, 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(13):1448–54.

    CAS  PubMed  Google Scholar 

  47. Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, et al. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): a multinational placebo-controlled phase II trial. J Clin Oncol. 2016;34(23):2728–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Fukuoka S, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M, 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). Journal of Clinical Oncology. 2020:JCO.19.03296.

  49. Yi JH, Lee J, Lee J, Park SH, Park JO, Yim DS, et al. Randomised phase II trial of docetaxel and sunitinib in patients with metastatic gastric cancer who were previously treated with fluoropyrimidine and platinum. Br J Cancer. 2012;106(9):1469–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Sun W, Powell M, O'Dwyer PJ, Catalano P, Ansari RH, Benson AB 3rd. Phase II study of sorafenib in combination with docetaxel and cisplatin in the treatment of metastatic or advanced gastric and gastroesophageal junction adenocarcinoma: ECOG 5203. J Clin Oncol. 2010;28(18):2947–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Sasore T, Kennedy B. Deciphering combinations of PI3K/AKT/mTOR pathway drugs augmenting anti-angiogenic efficacy in vivo. PLoS One. 2014;9(8):e105280.

    PubMed  PubMed Central  Google Scholar 

  52. Li VS, Wong CW, Chan TL, Chan AS, Zhao W, Chu KM, et al. Mutations of PIK3CA in gastric adenocarcinoma. BMC Cancer. 2005;5:29.

    PubMed  PubMed Central  Google Scholar 

  53. Al-Batran SE, Ducreux M, Ohtsu A. mTOR as a therapeutic target in patients with gastric cancer. Int J Cancer. 2012;130(3):491–6.

    CAS  PubMed  Google Scholar 

  54. Doi T, Muro K, Boku N, Yamada Y, Nishina T, Takiuchi H, et al. Multicenter phase II study of everolimus in patients with previously treated metastatic gastric cancer. J Clin Oncol. 2010;28(11):1904–10.

    CAS  PubMed  Google Scholar 

  55. Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, et al. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol. 2013;31(31):3935–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Gherardi E, Birchmeier W, Birchmeier C, Vande WG. Targeting MET in cancer: rationale and progress. Nat Rev Cancer. 2012;12(2):89–103.

    CAS  PubMed  Google Scholar 

  57. Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer. 1999;85(9):1894–902.

    CAS  PubMed  Google Scholar 

  58. Taniguchi K, Yonemura Y, Nojima N, Hirono Y, Fushida S, Fujimura T, et al. The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor. Cancer. 1998;82(11):2112–22.

    CAS  PubMed  Google Scholar 

  59. Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, 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(11):1467–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Shah MA, Bang YJ, Lordick F, Alsina M, Chen M, Hack SP, 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):620–7.

    PubMed  Google Scholar 

  61. Curtin NJ. PARP inhibitors target ATM+p53-defective gastric cancer. Cell Cycle. 2014;13(20):3161–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Kurz EU, Lees-Miller SP. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst). 2004;3(8–9):889–900.

    CAS  Google Scholar 

  63. Bang YJ, Im SA, Lee KW, Cho JY, Song EK, Lee KH, et al. Randomized, double-blind phase II trial with prospective classification by ATM protein level to evaluate the efficacy and tolerability of olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer. J Clin Oncol. 2015;33(33):3858–65.

    CAS  PubMed  Google Scholar 

  64. Kim HS, Kim MA, Hodgson D, Harbron C, Wellings R, O'Connor MJ, et al. Concordance of ATM (ataxia telangiectasia mutated) immunohistochemistry between biopsy or metastatic tumor samples and primary tumors in gastric cancer patients. Pathobiology. 2013;80(3):127–37.

    CAS  PubMed  Google Scholar 

  65. O'Connor MJ. Targeting the DNA damage response in cancer. Mol Cell. 2015;60(4):547–60.

    CAS  PubMed  Google Scholar 

  66. Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, 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(12):1637–51.

    CAS  PubMed  Google Scholar 

  67. Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012;366(26):2517–9.

    CAS  PubMed  Google Scholar 

  68. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, 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(10111):2461–71.

    CAS  PubMed  Google Scholar 

  70. Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, et al. CheckMate-032 study: efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer. J Clin Oncol. 2018;36(28):2836–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, 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(5):e180013.

    PubMed  PubMed Central  Google Scholar 

  72. • Shitara K, Ozguroglu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, 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(10142):123–33 This study resulted in the FDA approval of the first immune therapy in gastric cancer.

    CAS  PubMed  Google Scholar 

  73. Kojima T, Muro K, Francois E, Hsu C-H, Moriwaki T, Kim S-B, et al. Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: phase III KEYNOTE-181 study. J Clin Oncol. 2019;37(4_suppl):2.

    Google Scholar 

  74. Tabernero J, Cutsem EV, Bang Y-J, Fuchs CS, Wyrwicz L, Lee KW, et al. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. J Clin Oncol. 2019;37(18_suppl):LBA4007–LBA.

    Google Scholar 

  75. Chung HC, Arkenau HT, Lee J, Rha SY, Oh DY, Wyrwicz L, et al. Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN solid tumor trial. J Immunother Cancer. 2019;7(1):30.

    PubMed  PubMed Central  Google Scholar 

  76. Doi T, Iwasa S, Muro K, Satoh T, Hironaka S, Esaki T, et al. Phase 1 trial of avelumab (anti-PD-L1) in Japanese patients with advanced solid tumors, including dose expansion in patients with gastric or gastroesophageal junction cancer: the JAVELIN solid tumor JPN trial. Gastric Cancer. 2019;22(4):817–27.

    CAS  PubMed  Google Scholar 

  77. Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, 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;29(10):2052–60.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Cecchini MD.

Ethics declarations

Conflict of Interest

Timil Patel does not have any conflicts of interest to disclose. Michael Cecchini has received compensation from AstraZeneca, Eisai, and Agios for service as a consultant. Michael Cecchini has received honoraria from AstraZeneca, Eisai, and Agios.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Upper Gastrointestinal Cancers

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patel, T.H., Cecchini, M. Targeted Therapies in Advanced Gastric Cancer. Curr. Treat. Options in Oncol. 21, 70 (2020). https://doi.org/10.1007/s11864-020-00774-4

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11864-020-00774-4

Keywords

Navigation