Advanced gastric cancer: Current treatment landscape and future perspectives

World Journal of Gastroenterology

Volumn 22, Issue 8, 2016, Pages 2403-2414

  DIgklia, Antonia ^a   Wagner, Anna Dorothea ^a  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

Author keywords

Chemotherapy; Clinical trials; Gastric cancer; Perspectives; Phase; Targeted therapy

Indexed keywords

ANTINEOPLASTIC METAL COMPLEX; CAPECITABINE; CAPECITABINE PLUS OXALIPLATIN; CISPLATIN; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 1; EPIRUBICIN; FLUOROPYRIMIDINE; FLUOROURACIL; GIMERACIL PLUS OTERACIL POTASSIUM PLUS TEGAFUR; IRINOTECAN; LAPATINIB; OXALIPLATIN; PACLITAXEL; PERTUZUMAB; TAXANE DERIVATIVE; TEGAFUR; TRASTUZUMAB; TRASTUZUMAB EMTANSINE; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT;

ADVANCED CANCER; ANGIOGENESIS; CANCER COMBINATION CHEMOTHERAPY; CANCER THERAPY; DRUG DEVELOPMENT; HEALTH CARE QUALITY; HUMAN; HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 POSITIVE GASTRIC CANCER; META ANALYSIS (TOPIC); MOLECULARLY TARGETED THERAPY; MONOTHERAPY; PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STOMACH CANCER; CANCER STAGING; DISEASE COURSE; DISEASE FREE SURVIVAL; GENETIC PREDISPOSITION; GENETICS; MOLECULAR DIAGNOSIS; MORTALITY; PALLIATIVE THERAPY; PATHOLOGY; PERSONALIZED MEDICINE; PHENOTYPE; PREDICTIVE VALUE; PROCEDURES; RISK FACTOR; STOMACH NEOPLASMS; TIME FACTOR; TREATMENT OUTCOME;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DISEASE PROGRESSION; DISEASE-FREE SURVIVAL; DRUG DISCOVERY; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MOLECULAR DIAGNOSTIC TECHNIQUES; MOLECULAR TARGETED THERAPY; NEOPLASM STAGING; PALLIATIVE CARE; PHENOTYPE; PRECISION MEDICINE; PREDICTIVE VALUE OF TESTS; RISK FACTORS; STOMACH NEOPLASMS; TIME FACTORS; TREATMENT OUTCOME;

EID: 84959926722     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v22.i8.2403     Document Type: Review

References (63)

1. Combined modality approaches to cancer therapy. Council on Scientific Affairs. JAMA 1984; 251: 2398-2407 [PMID: 6323778]
2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-2917 [PMID: 21351269 DOI: 10.1002/ijc.25516]
3. Forman D, Burley VJ. Gastric cancer: global pattern of the disease and an overview of environmental risk factors. Best Pract Res Clin Gastroenterol 2006; 20: 633-649 [PMID: 16997150 DOI: 10.1016/j.bpg.2006.04.008]
4. Polkowski W, van Sandick JW, Offerhaus GJ, ten Kate FJ, Mulder J, Obertop H, van Lanschot JJ. Prognostic value of Laurén classification and c-erbB-2 oncogene overexpression in adenocarcinoma of the esophagus and gastroesophageal junction. Ann Surg Oncol 1999; 6: 290-297 [PMID: 10340889]
5. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001; 345: 784-789 [PMID: 11556297 DOI: 10.1056/NEJMoa001999]
6. Deng N, Goh LK, Wang H, Das K, Tao J, Tan IB, Zhang S, Lee M, Wu J, Lim KH, Lei Z, Goh G, Lim QY, Tan AL, Sin Poh DY, Riahi S, Bell S, Shi MM, Linnartz R, Zhu F, Yeoh KG, Toh HC, Yong WP, Cheong HC, Rha SY, Boussioutas A, Grabsch H, Rozen S, Tan P. 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 [PMID: 22315472 DOI: 10.1136/gutjnl-2011-301839]
7. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014; 513: 202-209 [PMID: 25079317 DOI: 10.1038/nature13480]
8. Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 2006; 24: 2903-2909 [PMID: 16782930 DOI: 10.1200/JCO.2005.05.0245]
9. Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, Fleig WE. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 2010; (3): CD004064 [PMID: 20238327 DOI: 10.1002/14651858.CD004064.pub3]
10. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 2008; 9: 215-221 [PMID: 18282805 DOI: 10.1016/S1470-2045(08)70035-4]
11. Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol 2009; 10: 1063-1069 [PMID: 19818685 DOI: 10.1016/S1470-2045(09)70259-1]
12. Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol 2009; 20: 666-673 [PMID: 19153121 DOI: 10.1093/annonc/mdn717]
13. Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol 2010; 28: 1547-1553 [PMID: 20159816 DOI: 10.1200/JCO.2009.25.4706]
14. Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, Nishina T, Amagai K, Chin K, Niwa Y, Tsuji A, Imamura H, Tsuda M, Yasui H, Fujii H, Yamaguchi K, Yasui H, Hironaka S, Shimada K, Miwa H, Hamada C, Hyodo I. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naéve patients with advanced gastric cancer. Ann Oncol 2015; 26: 141-148 [PMID: 25316259 DOI: 10.1093/annonc/mdu472]
15. Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol 2008; 26: 1435-1442 [PMID: 18349393 DOI: 10.1200/JCO.2007.13.9378]
16. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008; 358: 36-46 [PMID: 18172173 DOI: 10.1056/NEJMoa073149]
17. Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol 2008; 19: 1450-1457 [PMID: 18558665 DOI: 10.1093/annonc/mdn166]
18. Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol 2010; 21: 71-77 [PMID: 19605504 DOI: 10.1093/annonc/mdp269]
19. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 2006; 24: 4991-4997 [PMID: 17075117 DOI: 10.1200/JCO.2006.06.8429]
20. Lorenzen S, Pauligk C, Homann N, Schmalenberg H, Jäger E, Al-Batran SE. Feasibility of perioperative chemotherapy with infusional 5-FU, leucovorin, and oxaliplatin with (FLOT) or without (FLO) docetaxel in elderly patients with locally advanced esophagogastric cancer. Br J Cancer 2013; 108: 519-526 [PMID: 23322206 DOI: 10.1038/bjc.2012.588]
21. Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol 2014; 140: 319-328 [PMID: 24366758 DOI: 10.1007/s00432-013-1563-5]
22. Van Cutsem E, Boni C, Tabernero J, Massuti B, Middleton G, Dane F, Reichardt P, Pimentel FL, Cohn A, Follana P, Clemens M, Zaniboni A, Moiseyenko V, Harrison M, Richards DA, Prenen H, Pernot S, Ecstein-Fraisse E, Hitier S, Rougier P. Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study. Ann Oncol 2015; 26: 149-156 [PMID: 25416687 DOI: 10.1093/annonc/mdu496]
23. Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, Gornet JM, Aparicio T, Nguyen S, Azzedine A, Etienne PL, Boucher E, Rebischung C, Hammel P, Rougier P, Bedenne L, Bouché O. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol 2014; 32: 3520-3526 [PMID: 25287828 DOI: 10.1200/JCO.2013.54.1011]
24. Al-Batran SE, Pauligk C, Homann N, Hartmann JT, Moehler M, Probst S, Rethwisch V, Stoehlmacher-Williams J, Prasnikar N, Hollerbach S, Bokemeyer C, Mahlberg R, Hofheinz RD, Luley K, Kullmann F, Jäger E. The feasibility of triple-drug chemotherapy combination in older adult patients with oesophagogastric cancer: a randomised trial of the Arbeitsgemeinschaft Internistische Onkologie (FLOT65+). Eur J Cancer 2013; 49: 835-842 [PMID: 23063354 DOI: 10.1016/j.ejca.2012.09.025]
25. Ajani JA, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Marabotti C, Van Cutsem E. Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: the V-325 Study Group. J Clin Oncol 2007; 25: 3205-3209 [PMID: 17664467 DOI: 10.1200/JCO.2006.10.4968]
26. Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 2012; 30: 1513-1518 [PMID: 22412140 DOI: 10.1200/JCO.2011.39.4585]
27. Kim HS, Kim HJ, Kim SY, Kim TY, Lee KW, Baek SK, Kim TY, Ryu MH, Nam BH, Zang DY. Second-line chemotherapy versus supportive cancer treatment in advanced gastric cancer: a metaanalysis. Ann Oncol 2013; 24: 2850-2854 [PMID: 23942775 DOI: 10.1093/annonc/mdt351]
28. Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer-a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 2011; 47: 2306-2314 [PMID: 21742485 DOI: 10.1016/j.ejca.2011.06.002]
29. Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol 2014; 15: 78-86 [PMID: 24332238 DOI: 10.1016/S1470-2045(13)70549-7]
30. Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol 2013; 31: 4438-4444 [PMID: 24190112 DOI: 10.1200/JCO.2012.48.5805]
31. Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N, Takeda Y, Moriwaki T, Amagai K, Sekikawa T, Sakuyama T, Kanda T, Sasaki T, Azuma M, Takahashi F, Takeuchi M, Koizumi W. Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer 2014; 50: 1437-1445 [PMID: 24560487 DOI: 10.1016/j.ejca.2014.01.020]
32. Kim C, Mulder K, Spratlin J. How prognostic and predictive biomarkers are transforming our understanDing and management of advanced gastric cancer. Oncologist 2014; 19: 1046-1055 [PMID: 25142842 DOI: 10.1634/theoncologist.2014-0006]
33. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK. 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 [PMID: 20728210 DOI: 10.1016/S0140-6736(10)61121-X]
34. Satoh T, Bang YJ, Gotovkin EA, Hamamoto Y, Kang YK, Moiseyenko VM, Ohtsu A, Van Cutsem E, Al-Sakaff N, Urspruch A, Hill J, Weber HA, Chung HC. Quality of life in the trastuzumab for gastric cancer trial. Oncologist 2014; 19: 712-719 [PMID: 24951609 DOI: 10.1634/theoncologist.2014-0058]
35. Chua C, Tan IB, Yamada Y, Rha SY, Yong WP, Ong WS, Tham CK, Ng M, Tai DW, Iwasa S, Lim HY, Choo SP. Phase II study of trastuzumab in combination with S-1 and cisplatin in the firstline treatment of human epidermal growth factor receptor HER2-positive advanced gastric cancer. Cancer Chemother Pharmacol 2015; 76: 397-408 [PMID: 26099969 DOI: 10.1007/s00280-015-2811-y]
36. Ryu MH, Yoo C, Kim JG, Ryoo BY, Park YS, Park SR, Han HS, Chung IJ, Song EK, Lee KH, Kang SY, Kang YK. Multicenter phase II study of trastuzumab in combination with capecitabine and oxaliplatin for advanced gastric cancer. Eur J Cancer 2015; 51: 482-488 [PMID: 25661103 DOI: 10.1016/j.ejca.2014.12.015]
37. Hegewisch-Becker SME, Kröning H, Petersen V, Hannig C, Pott D, et al. Trastuzumab (TRA) in combination with different firstline chemotherapies for treatment of HER2-positive metastatic gastric or gastroesophageal junction cancer (MGC): findings from the German noninterventional observational study HerMES. 2012 ASCO Annual Meeting, 2012
38. Paul B, Trovato JA, Thompson J. Lapatinib: a dual tyrosine kinase inhibitor for metastatic breast cancer. Am J Health Syst Pharm 2008; 65: 1703-1710 [PMID: 18768996 DOI: 10.2146/ajhp070646]
39. Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. Lapatinib plus paclitaxel versus paclitaxel alone in the secondline treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN-a randomized, phase III study. J Clin Oncol 2014; 32: 2039-2049 [PMID: 24868024 DOI: 10.1200/JCO.2013.53.6136]
40. Hecht JRB, Qin YJ, Chung S, Xu HC, Park JM, 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. 2013 ASCO annual meeting, 2013
41. Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebocontrolled, phase 3 study. Lancet Oncol 2013; 14: 461-471 [PMID: 23602601 DOI: 10.1016/S1470-2045(13)70130-X]
42. Yamashita-Kashima Y, Iijima S, Yorozu K, Furugaki K, Kurasawa M, Ohta M, Fujimoto-Ouchi K. Pertuzumab in combination with trastuzumab shows significantly enhanced antitumor activity in HER2-positive human gastric cancer xenograft models. Clin Cancer Res 2011; 17: 5060-5070 [PMID: 21700765 DOI: 10.1158/1078-0432.CCR-10-2927]
43. Kang YK, Rha SY, Tassone P, Barriuso J, Yu R, Szado T, Garg A, Bang YJ. 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: 660-666 [PMID: 24960402 DOI: 10.1038/bjc.2014.356]
44. Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M. 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 [PMID: 23594786 DOI: 10.1016/S1470-2045(13)70102-5]
45. Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, Ferry D, Mansoor W, Crosby T, Coxon F, Smith D, Waters J, Iveson T, Falk S, Slater S, Peckitt C, Barbachano Y. 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 [PMID: 23594787 DOI: 10.1016/S1470-2045(13)70096-2]
46. Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Eberhardt WE, de Marinis F, Heeger S, Goddemeier T, O'Byrne KJ, Gatzemeier U. Prognostic factors in patients with advanced non-small cell lung cancer: data from the phase III FLEX study. Lung Cancer 2012; 77: 376-382 [PMID: 22498112 DOI: 10.1016/j.lungcan.2012.03.010]
47. Satoh T, Lee KH, Rha SY, Sasaki Y, Park SH, Komatsu Y, Yasui H, Kim TY, Yamaguchi K, Fuse N, Yamada Y, Ura T, Kim SY, Munakata M, Saitoh S, Nishio K, Morita S, Yamamoto E, Zhang Q, Kim JM, Kim YH, Sakata Y. Randomized phase II trial of nimotuzumab plus irinotecan versus irinotecan alone as second-line therapy for patients with advanced gastric cancer. Gastric Cancer 2015; 18: 824-832 [PMID: 25185971 DOI: 10.1007/s10120-014-0420-9]
48. Song ZJ, Gong P, Wu YE. Relationship between the expression of iNOS,VEGF,tumor angiogenesis and gastric cancer. World J Gastroenterol 2002; 8: 591-595 [PMID: 12174362 DOI: 10.3748/wjg.v8.i4.591]
49. Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M, Sawada T, Sowa M. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer 1996; 77: 858-863 [PMID: 8608475]
50. Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as firstline therapy in advanced gastric cancer: a randomized, doubleblind, placebo-controlled phase III study. J Clin Oncol 2011; 29: 3968-3976 [PMID: 21844504 DOI: 10.1200/JCO.2011.36.2236]
51. Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J. 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: 31-39 [PMID: 24094768 DOI: 10.1016/S0140-6736(13)61719-5]
52. Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A. 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 [PMID: 25240821 DOI: 10.1016/S1470-2045(14)70420-6]
53. Qin S. Phase III study of apatinib in advanced gastric cancer: A randomized, double-blind, placebo-controlled trial. 2014 ASCO Annual Meeting, 2014
54. Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, Sahmoud T, Shen L, Yeh KH, Chin K, Muro K, Kim YH, Ferry D, Tebbutt NC, Al-Batran SE, Smith H, Costantini C, Rizvi S, Lebwohl D, Van Cutsem E. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol 2013; 31: 3935-3943 [PMID: 24043745 DOI: 10.1200/JCO.2012.48.3552]
55. Kijima Y, Hokita S, Yoshinaka H, Itoh T, Koriyama C, Eizuru Y, Akiba S, Aikou T. Amplification and overexpression of c-met gene in Epstein-Barr virus-associated gastric carcinomas. Oncology 2002; 62: 60-65 [PMID: 11810045]
56. Soman NR, Correa P, Ruiz BA, Wogan GN. The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions. Proc Natl Acad Sci USA 1991; 88: 4892-4896 [PMID: 2052572]
57. Iveson T, Donehower RC, Davidenko I, Tjulandin S, Deptala A, Harrison M, Nirni S, Lakshmaiah K, Thomas A, Jiang Y, Zhu M, Tang R, Anderson A, Dubey S, Oliner KS, Loh E. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol 2014; 15: 1007-1018 [PMID: 24965569 DOI: 10.1016/S1470-2045(14)70023-3]
58. Zhu M, Tang R, Doshi S, Oliner KS, Dubey S, Jiang Y, Donehower RC, Iveson T, Loh EY, Zhang Y. Exposure-response analysis of rilotumumab in gastric cancer: the role of tumour MET expression. Br J Cancer 2015; 112: 429-437 [PMID: 25584489 DOI: 10.1038/bjc.2014.649]
59. Cunningham D, Davidenko I, Ilson DH, Murad AM, Tebbutt NC, Jiang Y, Loh E, Dubey S. RILOMET-1: An international phase III multicenter, randomized, double-blind, placebo-controlled trial of rilotumumab plus epirubicin, cisplatin, and capecitabine (ECX) as first-line therapy in patients with advanced MET-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. 2013 ASCO Annual Meeting, 2015
60. Shah MA, Lordick F, Tabernero J, Chen M, Hack SP, Phan SC, Shames DS, Cunningham D. METGastric: A phase III study of onartuzumab plus mFOLFOX6 in patients with metastatic HER2-negative (HER2-) and MET-positive (MET ) adenocarcinoma of the stomach or gastroesophageal junction (GEC). 2015 ASCO Annual Meeting, 2015
61. McDermott J, Jimeno A. Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer. Drugs Today (Barc) 2015; 51: 7-20 [PMID: 25685857 DOI: 10.1358/dot.2015.51.1.2250387]
62. Muro KBY, Shankaran V, Geva R, Catenacci DVT, Gupta S, Eder JP, Berger R, Gonzalez EJ, Pulini J, Ray AB, Dolled-Filhart M, Emancipator K, Pathiraja K, Shu X, Koshiji MR, Cheng JD, Chung HC. A phase 1B study of pembrolizumab in patients with advanced gastric cancer. (Abstract LBA15). ESMO Annual Meeting, 2014
63. Bang YJ, Shankaran V, Geva R, Catenacci DVT, Gupta S, Eder JP, Berger R, Gonzalez EJ, Ray A, Dolled-Filhart M, Emancipator K, Pathiraja K, Lunceford JK, Cheng JD, Koshiji M, Muro K. Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in KEYNOTE-012. 2015 ASCO Annual Meeting, 2015