Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
권호 표지
DOI QR코드

DOI QR Code

A Comprehensive and Comparative Review of Global Gastric Cancer Treatment Guidelines

  • Received : 2022.02.25
  • Accepted : 2022.03.19
  • Published : 2022.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Countries differ in their treatment expertise and research results regarding gastric cancer; hence, treatment guidelines are diverse based on evidence and medical situations. A comprehensive and comparative review of each country's guidelines is imperative to understand the similarities and differences among countries. We reviewed and compared five gastric cancer treatment guidelines in terms of endoscopic, surgical, perioperative, and palliative systemic treatment based on evidence levels and recommendation grades, as well as the postoperative follow-up strategies for each guideline. The Korean, Chinese, and European guidelines provided evidence and grading of the recommendations. The United States guidelines suggested categories for evidence and consensus. The Japanese guidelines suggested evidence and recommendations only for systemic treatment. The Korean and Japanese guidelines described endoscopic treatment, surgery, and lymphadenectomy in detail. The Chinese, United States, and European guidelines more intensively considered perioperative chemotherapy. In particular, the indications for chemotherapy and the regimens recommended by each guideline differed slightly. Considering their medical situations, each guideline had some diversity in terms of adopting evidence, which resulted in heterogeneous recommendations. This review will help medical personnel to comprehensively understand the diversity in gastric cancer treatment guidelines for each country in terms of evidence and recommendations.

Keywords

Acknowledgement

This research was supported by a grant from the Korea Health Technology R&D Project, through the Korea Health Industry Development Institute (KHIDI) (grant numbers: HI19C0481, HC20C0155), funded by the Ministry of Health & Welfare, Republic of Korea.

References

  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;68:394-424. https://doi.org/10.3322/caac.21492
  2. GBD 2017 Stomach Cancer Collaborators. The global, regional, and national burden of stomach cancer in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease study 2017. Lancet Gastroenterol Hepatol 2020;5:42-54. https://doi.org/10.1016/s2468-1253(19)30328-0
  3. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Niksic M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 2018;391:1023-1075. https://doi.org/10.1016/S0140-6736(17)33326-3
  4. Information Committee of the Korean Gastric Cancer Association. Korean Gastric Cancer AssociationLed nationwide survey on surgically treated gastric cancers in 2019. J Gastric Cancer 2021;21:221-235. https://doi.org/10.5230/jgc.2021.21.e27
  5. Jun JK, Choi KS, Lee HY, Suh M, Park B, Song SH, et al. Effectiveness of the Korean National Cancer Screening Program in reducing gastric cancer mortality. Gastroenterology 2017;152:1319-1328.e7. https://doi.org/10.1053/j.gastro.2017.01.029
  6. Hamashima CSystematic Review Group and Guideline Development Group for Gastric Cancer Screening Guidelines. Update version of the Japanese Guidelines for Gastric Cancer Screening. Jpn J Clin Oncol 2018;48:673-683. https://doi.org/10.1093/jjco/hyy077
  7. Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev 2014;23:700-713. https://doi.org/10.1158/1055-9965.EPI-13-1057
  8. Guideline Committee of the Korean Gastric Cancer Association (KGCA), Development Working Group & Review Panel. Development Working Group & Review Panel. Korean practice guideline for gastric cancer 2018: an evidence-based, multi-disciplinary approach. J Gastric Cancer 2019;19:1-48. https://doi.org/10.5230/jgc.2019.19.e8
  9. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer 2021;24:1-21. https://doi.org/10.1007/s10120-020-01042-y
  10. Wang FH, Zhang XT, Li YF, Tang L, Qu XJ, Ying JE, et al. The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer, 2021. Cancer Commun (Lond) 2021;41:747-795. https://doi.org/10.1002/cac2.12193
  11. National Comprehensive Cancer Network. NCCN guideline: gastric cancer (version 3.2021) [Internet]. Plymouth Meeting (PA): National Comprehensive Cancer Network; 2021 [cited 2021 Jul 13]. Available from: http://www.nccn.org.
  12. Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D, et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016;27:v38-v49. https://doi.org/10.1093/annonc/mdw350
  13. Kim YI, Kim YA, Kim CG, Ryu KW, Kim YW, Sim JA, et al. Serial intermediate-term quality of life comparison after endoscopic submucosal dissection versus surgery in early gastric cancer patients. Surg Endosc 2018;32:2114-2122. https://doi.org/10.1007/s00464-017-5909-y
  14. Facciorusso A, Antonino M, Di Maso M, Muscatiello N. Endoscopic submucosal dissection vs endoscopic mucosal resection for early gastric cancer: a meta-analysis. World J Gastrointest Endosc 2014;6:555-563. https://doi.org/10.4253/wjge.v6.i11.555
  15. Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T, Repici A, Vieth M, De Ceglie A, et al. Endoscopic submucosal dissection: European society of gastrointestinal endoscopy (ESGE) guideline. Endoscopy 2015;47:829-854. https://doi.org/10.1055/s-0034-1392882
  16. Nishizawa T, Yahagi N. Long-term outcomes of using endoscopic submucosal dissection to treat early gastric cancer. Gut Liver 2018;12:119-124. https://doi.org/10.5009/gnl17095
  17. Min BH, Kim ER, Kim KM, Park CK, Lee JH, Rhee PL, et al. Surveillance strategy based on the incidence and patterns of recurrence after curative endoscopic submucosal dissection for early gastric cancer. Endoscopy 2015;47:784-793. https://doi.org/10.1055/s-0034-1392249
  18. Kim TS, Min BH, Kim KM, Lee JH, Rhee PL, Kim JJ. Endoscopic submucosal dissection for papillary adenocarcinoma of the stomach: low curative resection rate but favorable long-term outcomes after curative resection. Gastric Cancer 2019;22:363-368. https://doi.org/10.1007/s10120-018-0857-3
  19. Takizawa K, Takashima A, Kimura A, Mizusawa J, Hasuike N, Ono H, et al. A phase II clinical trial of endoscopic submucosal dissection for early gastric cancer of undifferentiated type: Japan Clinical Oncology Group study JCOG1009/1010. Jpn J Clin Oncol 2013;43:87-91. https://doi.org/10.1093/jjco/hys189
  20. Choi JY, Jeon SW, Cho KB, Park KS, Kim ES, Park CK, et al. Non-curative endoscopic resection does not always lead to grave outcomes in submucosal invasive early gastric cancer. Surg Endosc 2015;29:1842-1849. https://doi.org/10.1007/s00464-014-3874-2
  21. Noh GY, Ku HR, Kim YJ, Park SC, Kim J, Han CJ, et al. Clinical outcomes of early gastric cancer with lymphovascular invasion or positive vertical resection margin after endoscopic submucosal dissection. Surg Endosc 2015;29:2583-2589. https://doi.org/10.1007/s00464-014-3973-0
  22. Toya Y, Endo M, Nakamura S, Akasaka R, Kosaka T, Yanai S, et al. Clinical outcomes of non-curative endoscopic submucosal dissection with negative resected margins for gastric cancer. Gastrointest Endosc 2017;85:1218-1224. https://doi.org/10.1016/j.gie.2016.11.018
  23. Suzuki S, Gotoda T, Hatta W, Oyama T, Kawata N, Takahashi A, et al. Survival benefit of additional surgery after non-curative endoscopic submucosal dissection for early gastric cancer: a propensity score matching analysis. Ann Surg Oncol 2017;24:3353-3360. https://doi.org/10.1245/s10434-017-6039-4
  24. Eom BW, Kim YI, Kim KH, Yoon HM, Cho SJ, Lee JY, et al. Survival benefit of additional surgery after noncurative endoscopic resection in patients with early gastric cancer. Gastrointest Endosc 2017;85:155-163.e3. https://doi.org/10.1016/j.gie.2016.07.036
  25. Hatta W, Gotoda T, Oyama T, Kawata N, Takahashi A, Yoshifuku Y, et al. A scoring system to stratify curability after endoscopic submucosal dissection for early gastric cancer: "eCura system". Am J Gastroenterol 2017;112:874-881. https://doi.org/10.1038/ajg.2017.95
  26. Yoo CH, Sohn BH, Han WK, Pae WK. Long-term results of proximal and total gastrectomy for adenocarcinoma of the upper third of the stomach. Cancer Res Treat 2004;36:50-55. https://doi.org/10.4143/crt.2004.36.1.50
  27. Ahn SH, Lee JH, Park DJ, Kim HH. Comparative study of clinical outcomes between laparoscopy-assisted proximal gastrectomy (LAPG) and laparoscopy-assisted total gastrectomy (LATG) for proximal gastric cancer. Gastric Cancer 2013;16:282-289. https://doi.org/10.1007/s10120-012-0178-x
  28. Masuzawa T, Takiguchi S, Hirao M, Imamura H, Kimura Y, Fujita J, et al. Comparison of perioperative and long-term outcomes of total and proximal gastrectomy for early gastric cancer: a multi-institutional retrospective study. World J Surg 2014;38:1100-1106. https://doi.org/10.1007/s00268-013-2370-5
  29. Jung DH, Lee Y, Kim DW, Park YS, Ahn SH, Park DJ, et al. Laparoscopic proximal gastrectomy with double tract reconstruction is superior to laparoscopic total gastrectomy for proximal early gastric cancer. Surg Endosc 2017;31:3961-3969. https://doi.org/10.1007/s00464-017-5429-9
  30. An JY, Youn HG, Choi MG, Noh JH, Sohn TS, Kim S. The difficult choice between total and proximal gastrectomy in proximal early gastric cancer. Am J Surg 2008;196:587-591. https://doi.org/10.1016/j.amjsurg.2007.09.040
  31. Huh YJ, Lee HJ, Oh SY, Lee KG, Yang JY, Ahn HS, et al. Clinical outcome of modified laparoscopy-assisted proximal gastrectomy compared to conventional proximal gastrectomy or total gastrectomy for upperthird early gastric cancer with special references to postoperative reflux esophagitis. J Gastric Cancer 2015;15:191-200. https://doi.org/10.5230/jgc.2015.15.3.191
  32. Toyomasu Y, Ogata K, Suzuki M, Yanoma T, Kimura A, Kogure N, et al. Restoration of gastrointestinal motility ameliorates nutritional deficiencies and body weight loss of patients who undergo laparoscopy-assisted proximal gastrectomy. Surg Endosc 2017;31:1393-1401. https://doi.org/10.1007/s00464-016-5127-z
  33. Takiguchi N, Takahashi M, Ikeda M, Inagawa S, Ueda S, Nobuoka T, et al. Long-term quality-of-life comparison of total gastrectomy and proximal gastrectomy by postgastrectomy syndrome assessment scale (PGSAS-45): a nationwide multi-institutional study. Gastric Cancer 2015;18:407-416. https://doi.org/10.1007/s10120-014-0377-8
  34. Ushimaru Y, Fujiwara Y, Shishido Y, Yanagimoto Y, Moon JH, Sugimura K, et al. Clinical outcomes of gastric cancer patients who underwent proximal or total gastrectomy: a propensity score-matched analysis. World J Surg 2018;42:1477-1484. https://doi.org/10.1007/s00268-017-4306-y
  35. Yoo CH, Sohn BH, Han WK, Pae WK. Proximal gastrectomy reconstructed by jejunal pouch interposition for upper third gastric cancer: prospective randomized study. World J Surg 2005;29:1592-1599. https://doi.org/10.1007/s00268-005-7793-1
  36. Suh YS, Han DS, Kong SH, Kwon S, Shin CI, Kim WH, et al. Laparoscopy-assisted pylorus-preserving gastrectomy is better than laparoscopy-assisted distal gastrectomy for middle-third early gastric cancer. Ann Surg 2014;259:485-493. https://doi.org/10.1097/sla.0b013e318294d142
  37. Xiao XM, Gaol C, Yin W, Yu WH, Qi F, Liu T. Pylorus-preserving versus distal subtotal gastrectomy for surgical treatment of early gastric cancer: a meta-analysis. Hepatogastroenterology 2014;61:870-879.
  38. Aizawa M, Honda M, Hiki N, Kinoshita T, Yabusaki H, Nunobe S, et al. Oncological outcomes of function-preserving gastrectomy for early gastric cancer: a multicenter propensity score matched cohort analysis comparing pylorus-preserving gastrectomy versus conventional distal gastrectomy. Gastric Cancer 2017;20:709-717. https://doi.org/10.1007/s10120-016-0644-y
  39. Schwarz RE, Smith DD. Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial. J Clin Oncol 2005;23:5404-5405. https://doi.org/10.1200/JCO.2005.05.189
  40. Cuschieri A, Weeden S, Fielding J, Bancewicz J, Craven J, Joypaul V, et al. Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Cooperative Group. Br J Cancer 1999;79:1522-1530. https://doi.org/10.1038/sj.bjc.6690243
  41. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol 2010;11:439-449. https://doi.org/10.1016/S1470-2045(10)70070-X
  42. Csendes A, Burdiles P, Rojas J, Braghetto I, Diaz JC, Maluenda F. A prospective randomized study comparing D2 total gastrectomy versus D2 total gastrectomy plus splenectomy in 187 patients with gastric carcinoma. Surgery 2002;131:401-407. https://doi.org/10.1067/msy.2002.121891
  43. Yu W, Choi GS, Chung HY. Randomized clinical trial of splenectomy versus splenic preservation in patients with proximal gastric cancer. Br J Surg 2006;93:559-563. https://doi.org/10.1002/bjs.5353
  44. Sano T, Sasako M, Mizusawa J, Yamamoto S, Katai H, Yoshikawa T, et al. Randomized controlled trial to evaluate splenectomy in total gastrectomy for proximal gastric carcinoma. Ann Surg 2017;265:277-283. https://doi.org/10.1097/SLA.0000000000001814
  45. Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, et al. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol 2016;17:309-318. https://doi.org/10.1016/S1470-2045(15)00553-7
  46. Kim HH, Han SU, Kim MC, Kim W, Lee HJ, Ryu SW, et al. Effect of laparoscopic distal gastrectomy vs open distal gastrectomy on long-term survival among patients with Stage I gastric cancer: the KLASS-01 randomized clinical trial. JAMA Oncol 2019;5:506-513. https://doi.org/10.1001/jamaoncol.2018.6727
  47. Nakamura K, Katai H, Mizusawa J, Yoshikawa T, Ando M, Terashima M, et al. A phase III study of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric Cancer (JCOG0912). Jpn J Clin Oncol 2013;43:324-327. https://doi.org/10.1093/jjco/hys220
  48. Katai H, Mizusawa J, Katayama H, Morita S, Yamada T, Bando E, et al. Survival outcomes after laparoscopy-assisted distal gastrectomy versus open distal gastrectomy with nodal dissection for clinical stage IA or IB gastric cancer (JCOG0912): a multicentre, non-inferiority, phase 3 randomised controlled trial. Lancet Gastroenterol Hepatol 2020;5:142-151. https://doi.org/10.1016/s2468-1253(19)30332-2
  49. Hyung WJ, Yang HK, Han SU, Lee YJ, Park JM, Kim JJ, et al. A feasibility study of laparoscopic total gastrectomy for clinical stage I gastric cancer: a prospective multi-center phase II clinical trial, KLASS 03. Gastric Cancer 2019;22:214-222. https://doi.org/10.1007/s10120-018-0864-4
  50. Katai H, Mizusawa J, Katayama H, Kunisaki C, Sakuramoto S, Inaki N, et al. Single-arm confirmatory trial of laparoscopy-assisted total or proximal gastrectomy with nodal dissection for clinical stage I gastric cancer: Japan Clinical Oncology Group study JCOG1401. Gastric Cancer 2019;22:999-1008. https://doi.org/10.1007/s10120-019-00929-9
  51. Liu F, Huang C, Xu Z, Su X, Zhao G, Ye J, et al. Morbidity and mortality of laparoscopic vs open total gastrectomy for clinical stage I gastric cancer: the CLASS02 multicenter randomized clinical trial. JAMA Oncol 2020;6:1590-1597. https://doi.org/10.1001/jamaoncol.2020.3152
  52. Hyung WJ, Yang HK, Park YK, Lee HJ, An JY, Kim W, et al. Long-term outcomes of laparoscopic distal gastrectomy for locally advanced gastric cancer: the KLASS-02-RCT randomized clinical trial. J Clin Oncol 2020;38:3304-3313. https://doi.org/10.1200/jco.20.01210
  53. Yu J, Huang C, Sun Y, Su X, Cao H, Hu J, et al. Effect of laparoscopic vs open distal gastrectomy on 3-year disease-free survival in patients with locally advanced gastric cancer: the CLASS-01 randomized clinical trial. JAMA 2019;321:1983-1992. https://doi.org/10.1001/jama.2019.5359
  54. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11-20. https://doi.org/10.1056/NEJMoa055531
  55. Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 2011;29:1715-1721. https://doi.org/10.1200/JCO.2010.33.0597
  56. Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, 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;393:1948-1957. https://doi.org/10.1016/S0140-6736(18)32557-1
  57. European Society for Medical Oncology. ESMO clinical practice guidelines: gastric cancer [Internet]. Lugano: European Society for Medical Oncology; c2022 [cited 2022 Jan 5]. Available from: https://www.esmo.org/guidelines/gastrointestinal-cancers/gastric-cancer.
  58. Ji J, Shen L, Li Z, Zhang X, Liang H, Xue Y, et al. Perioperative chemotherapy of oxaliplatin combined with S-1 (SOX) versus postoperative chemotherapy of SOX or oxaliplatin with capecitabine (XELOX) in locally advanced gastric adenocarcinoma with D2 gastrectomy: a randomized phase III trial (RESOLVE trial). Ann Oncol 2019;30:v877.
  59. Kang YK, Yook JH, Park YK, Kim YW, Kim J, Ryu MH, et al. Phase III randomized study of neoadjuvant chemotherapy (CT) with docetaxel (D), oxaliplatin (O) and S-1 (S)(DOS) followed by surgery and adjuvant S-1, vs surgery and adjuvant S-1, for resectable advanced gastric cancer (GC) (PRODIGY). Ann Oncol 2019;30:v876-v877.
  60. Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 2012;379:315-321. https://doi.org/10.1016/S0140-6736(11)61873-4
  61. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 2007;357:1810-1820. https://doi.org/10.1056/NEJMoa072252
  62. Yoshida K, Kodera Y, Kochi M, Ichikawa W, Kakeji Y, Sano T, et al. Addition of docetaxel to oral fluoropyrimidine improves efficacy in patients with Stage III gastric cancer: interim analysis of JACCRO GC-07, a randomized controlled trial. J Clin Oncol 2019;37:1296-1304. https://doi.org/10.1200/JCO.18.01138
  63. Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725-730. https://doi.org/10.1056/NEJMoa010187
  64. Park SH, Lim DH, Sohn TS, Lee J, Zang DY, Kim ST, et al. A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial. Ann Oncol 2021;32:368-374. https://doi.org/10.1016/j.annonc.2020.11.017
  65. Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol 2018;19:616-628. https://doi.org/10.1016/S1470-2045(18)30132-3
  66. Wagner AD, Syn NL, Moehler M, Grothe W, Yong WP, Tai BC, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 2017;8:CD004064.
  67. Glimelius B, Ekstrom K, Hoffman K, Graf W, Sjoden PO, Haglund U, et al. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 1997;8:163-168. https://doi.org/10.1023/A:1008243606668
  68. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008;358:36-46. https://doi.org/10.1056/NEJMoa073149
  69. Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, et al. 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. https://doi.org/10.1093/annonc/mdn717
  70. Okines AF, Norman AR, McCloud P, Kang YK, Cunningham D. Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracilbased combination chemotherapy for the treatment of advanced oesophago-gastric cancer. Ann Oncol 2009;20:1529-1534. https://doi.org/10.1093/annonc/mdp047
  71. Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, et al. 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. https://doi.org/10.1016/s1470-2045(09)70259-1
  72. Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, et al. 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. https://doi.org/10.1200/JCO.2009.25.4706
  73. 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;376:687-697. https://doi.org/10.1016/S0140-6736(10)61121-X
  74. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. 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. https://doi.org/10.1016/S1470-2045(08)70035-4
  75. 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;29:3968-3976. https://doi.org/10.1200/JCO.2011.36.2236
  76. Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, et al. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naive patients with advanced gastric cancer. Ann Oncol 2015;26:141-148. https://doi.org/10.1093/annonc/mdu472
  77. Lee KW, Chung IJ, Ryu MH, Park YI, Nam BH, Oh HS, et al. Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial). Gastric Cancer 2021;24:156-167. https://doi.org/10.1007/s10120-020-01101-4
  78. Xu R, Wang ZQ, Shen L, Wang W, Lu JW, Dai G, et al. S-1 plus oxaliplatin versus S-1 plus cisplatin as first-line treatment for advanced diffuse-type or mixed-type gastric/gastroesophageal junction adenocarcinoma: a randomized, phase 3 trial. J Clin Oncol 2019;37:4017. https://doi.org/10.1200/jco.2019.37.15_suppl.4017
  79. Hall PS, Swinson D, Cairns DA, Waters JS, Petty R, Allmark C, et al. Efficacy of reduced-intensity chemotherapy with oxaliplatin and capecitabine on quality of life and cancer control among older and frail patients with advanced gastroesophageal cancer: the GO2 Phase 3 randomized clinical trial. JAMA Oncol 2021;7:869-877. https://doi.org/10.1001/jamaoncol.2021.0848
  80. Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, et al. 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. https://doi.org/10.1200/JCO.2007.13.9378
  81. 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;27:2196-2203. https://doi.org/10.1093/annonc/mdw423
  82. Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, et al. 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. https://doi.org/10.1007/s00432-013-1563-5
  83. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. 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. https://doi.org/10.1200/JCO.2006.06.8429
  84. Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, 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;398:27-40. https://doi.org/10.1016/S0140-6736(21)00797-2
  85. Kurokawa Y, Sugimoto N, Miwa H, Tsuda M, Nishina S, Okuda H, et al. Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1). Br J Cancer 2014;110:1163-1168. https://doi.org/10.1038/bjc.2014.18
  86. Miura Y, Sukawa Y, Hironaka S, Mori M, Nishikawa K, Tokunaga S, et al. Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2-positive gastric cancer: a phase II trial and biomarker study (WJOG7212G). Gastric Cancer 2018;21:84-95. https://doi.org/10.1007/s10120-017-0725-6
  87. Ryu MH, Yoo C, Kim JG, Ryoo BY, Park YS, Park SR, et al. Multicenter phase II study of trastuzumab in combination with capecitabine and oxaliplatin for advanced gastric cancer. Eur J Cancer 2015;51:482-488. https://doi.org/10.1016/j.ejca.2014.12.015
  88. Yuki S, Shinozaki K, Kashiwada T, Kusumoto T, Iwatsuki M, Satake H, et al. Multicenter phase II study of SOX plus trastuzumab for patients with HER2+ metastatic or recurrent gastric cancer: KSCC/HGCSG/CCOG/PerSeUS 1501B. Cancer Chemother Pharmacol 2020;85:217-223. https://doi.org/10.1007/s00280-019-03991-3
  89. Rivera F, Romero C, Jimenez-Fonseca P, Izquierdo-Manuel M, Salud A, Martinez E, et al. Phase II study to evaluate the efficacy of trastuzumab in combination with capecitabine and oxaliplatin in first-line treatment of HER2-positive advanced gastric cancer: HERXO trial. Cancer Chemother Pharmacol 2019;83:1175-1181. https://doi.org/10.1007/s00280-019-03820-7
  90. Chung HC, Bang YJ, S Fuchs C, Qin SK, Satoh T, Shitara K, et al. First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. Future Oncol 2021;17:491-501. https://doi.org/10.2217/fon-2020-0737
  91. Janjigian YY, Kawazoe A, Yanez P, Li N, Lonardi S, Kolesnik O, et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature 2021;600:727-730. https://doi.org/10.1038/s41586-021-04161-3
  92. Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, et al. 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. https://doi.org/10.1016/j.ejca.2011.06.002
  93. Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, et al. 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. https://doi.org/10.1200/JCO.2011.39.4585
  94. Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, et al. 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. https://doi.org/10.1016/S1470-2045(13)70549-7
  95. Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, et al. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol 2013;24:1567-1573. https://doi.org/10.1093/annonc/mdt002
  96. 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;15:1224-1235. https://doi.org/10.1016/S1470-2045(14)70420-6
  97. 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;383:31-39. https://doi.org/10.1016/S0140-6736(13)61719-5
  98. Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, et al. Nab-paclitaxel versus solventbased paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol 2017;2:277-287. https://doi.org/10.1016/S2468-1253(16)30219-9
  99. Lee MJ, Hwang IG, Jang JS, Choi JH, Park BB, Chang MH, et al. Outcomes of third-line docetaxel-based chemotherapy in advanced gastric cancer who failed previous oxaliplatin-based and irinotecan-based chemotherapies. Cancer Res Treat 2012;44:235-241. https://doi.org/10.4143/crt.2012.44.4.235
  100. Fanotto V, Uccello M, Pecora I, Rimassa L, Leone F, Rosati G, et al. Outcomes of advanced gastric cancer patients treated with at least three lines of systemic chemotherapy. Oncologist 2017;22:1463-1469. https://doi.org/10.1634/theoncologist.2017-0158
  101. Choi IS, Choi M, Lee JH, Kim JH, Suh KJ, Lee JY, et al. Treatment patterns and outcomes in patients with metastatic gastric cancer receiving third-line chemotherapy: a population-based outcomes study. PLoS One 2018;13:e0198544. https://doi.org/10.1371/journal.pone.0198544
  102. Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, 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. https://doi.org/10.1016/S1470-2045(18)30739-3
  103. 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;390:2461-2471. https://doi.org/10.1016/S0140-6736(17)31827-5
  104. Muro K, Chung HC, Shankaran V, Geva R, Catenacci D, Gupta S, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol 2016;17:717-726. https://doi.org/10.1016/S1470-2045(16)00175-3
  105. Bang YJ, Kang YK, Catenacci DV, Muro K, Fuchs CS, Geva R, 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;22:828-837. https://doi.org/10.1007/s10120-018-00909-5
  106. Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, et al. Trastuzumab Deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med 2020;382:2419-2430. https://doi.org/10.1056/NEJMoa2004413
  107. Eom BW, Koo DH, An JY, Lee HH, Kim HI, Hur H, et al. Prospective multicentre randomised clinical trial comparing survival rates, quality of life and nutritional status between advanced gastric cancer patients with different follow-up intensities: study protocol for the STOFOLUP trial. BMJ Open 2021;11:e056187. https://doi.org/10.1136/bmjopen-2021-056187