Recent trend in gastric cancer treatment in the USA

Abstract

Gastric adenocarcinoma (GAC) is estimated as the fifteenth most common cancer in the USA. Incidence rate has been gradually decreasing, but prognosis remains dismal. For patients with locally advanced GAC (stage > T1B and < T4B), multimodality therapies, such as surgery, chemotherapy, and radiation therapy, are needed. Perioperative chemotherapy or postoperative chemoradiation/chemotherapy is recommended. For metastatic GAC patients, combination of two cytotoxics (platinum compound and fluoropyrimidine) has become a common place in the USA, and when HER2 is positive, trastuzumab is added. When GAC progresses after the first line therapy, additional biomarkers (microsatellite instability and programmed death ligand 1) should be tested so that checkpoint inhibitors can be used. Overall, the options for advanced GAC patients are limited and more research is needed.

Keywords

Gastric adenocarcinoma / chemotherapy / chemoradiation / preoperative treatment

References

[1] Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (editors). SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Based on November 2016 SEER data submission, posted to the SEER web site, April 2017. Available from: https://seer.cancer.gov/csr/1975_2014/ [Last accessed on 10 Apr 2018]

[2] Blot WJ,Kneller RW.Rising incidence of adenocarcinoma of the esophagus and gastric cardia..JAMA1991;265:1287-9

[3] Japanese Gastric Cancer Association..Japanese gastric cancer treatment guidelines 2014 (ver. 4)..Gastric Cancer2017;20:1-19 PMCID:PMC5215069

[4] Elimova E.Surgical resection first for localized gastric adenocarcinoma: are there adjuvant options?.J Clin Oncol2015;33:3085-91

[5] Elimova E,Chen HC,Shiozaki H,Charalampakis N,Harada K,Estrella JS,Sagebiel T,Weston B,Murphy MB,Minsky B,Mansfield PF,Ajani JA.Patterns of relapse in patients with localized gastric adenocarcinoma who had surgery with or without adjunctive therapy: costs and effectiveness of surveillance..Oncotarget2017;8:81430-40 PMCID:PMC5655297

[6] Macdonald JS,Benedetti J,Estes NC,Haller DG,Gunderson LL,Martenson JA.Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction..N Engl J Med2001;345:725-30

[7] Smalley SR,Haller DG,Estes NC,Gunderson LL,Martenson JA,Stemmermann GN,Macdonald JS.Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection..J Clin Oncol2012;30:2327-33 PMCID:PMC4517071

[8] Lee J,Kim S,Park JO,Lim HY,Sohn TS,Bae JM,Sohn I,Park CK,Kang WK.Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial..J Clin Oncol2012;30:268-73

[9] Verheij M,Cats A,Aaronson NK,Lind PA,Nordsmark M,Trip AK,Sikorska K,Van De Velde CJH.A multicenter randomized phase III trial of neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy in resectable gastric cancer: first results from the CRITICS study..J Clin Oncol2016;34 Suppl 15:abstr4000

[10] Lee HS,Hur WJ,Kwon HC,Kim JS,Jung GJ.Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: adjuvant 5-FU/cisplatin and chemoradiation with capecitabine..World J Gastroenterol2006;12:603-7 PMCID:PMC4066094

[11] Leong T,Willis D,Spry N,Di Iulio J,Mann GB.Adjuvant chemoradiation for gastric cancer using epirubicin, cisplatin, and 5-fluorouracil before and after three-dimensional conformal radiotherapy with concurrent infusional 5-fluorouracil: a multicenter study of the Trans-Tasman Radiation Oncology Group..Int J Radiat Oncol Biol Phys2011;79:690-5

[12] Fuchs CS,Niedzwiecki D,Mamon HJ,Haller DG,Alberts SR,Willett CG,Goldberg RM,Mayer RJ.Postoperative adjuvant chemoradiation for gastric or gastroesophageal junction (GEJ) adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (CRT) compared with bolus 5-FU/LV before and after CRT: intergroup trial CALGB 80101..J Clin Oncol2011;29 Suppl 15:abstr4003

[13] Cunningham D,Stenning SP,Van de Velde CJ,Scarffe JH,Falk SJ,Smith DB,Verma M,Chua YJ.Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer..N Engl J Med2006;355:11-20

[14] Ychou M,Pignon JP,Bouche O,Ducourtieux M,Fabre JM,Geneve J,Rougier P.Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial..J Clin Oncol2011;29:1715-21

[15] Alderson D,Nankivell MG,Griffin M,Grabsch HI,Goldstein C,Thompson J,Coxon FY,Langer R,Cunningham D.Neoadjuvant chemotherapy for resectable oesophageal and junctional adenocarcinoma: results from the UK Medical Research Council randomised OEO5 trial (ISRCTN 01852072)..J Clin Oncol2015;33 Suppl 15:abstr4002

[16] Al-Batran SE,Homann N,Kopp HG,Luley K,Probst S,Trojan J,Lindig U,Kasper S,Goetze T,Jaeger E.LBA27_PR: Docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) for resectable esophagogastric cancer: updated results from multicenter, randomized phase 3 FLOT4-AIO trial (German Gastric Group at AIO)..Ann Oncol2017;28 Suppl 5:mdx440.019

[17] Al-Batran SE,Schmalenberg H,Haag GM,Schmiegel WH,Probst S,Thuss-Patience PC,Trojan J,Pauligk C,Jaeger E,Schuler MH.Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): a multicenter, randomized phase 3 trial..J Clin Oncol2017;35 Suppl 15:abstr4004

[18] Ajani JA,Janjan N,Pisters PW,Feig B,Nivers R,Gunderson LL.Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma..J Clin Oncol2004;22:2774-80

[19] Ajani JA,Crane CH,Lunagomez S,Janjan N,Faust J,Nivers R,Pisters PW.Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome..J Clin Oncol2005;23:1237-44

[20] Ajani JA,Okawara GS,Pisters PW,Greskovich JF,Bradley JD,Rich TA.Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response..J Clin Oncol2006;24:3953-8

[21] Leong T,Michael M,Boussioutas A,Simes J,Haustermans K,Schuhmacher C,Darling G.TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG)..BMC Cancer2015;15:532 PMCID:PMC4507314

[22] Bang YJ,Feyereislova A,Shen L,Lordick F,Omuro Y,Aprile G,Hill J,Rüschoff J.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..Lancet2010;376:687-97

[23] Guimbaud R,Ries P,Maillard E,Gornet JM,Nguyen S,Etienne PL,Rebischung C,Rougier P,Bouche O.Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Federation Francophone de Cancerologie Digestive, Federation Nationale des Centres de Lutte Contre le Cancer, and Groupe Cooperateur Multidisciplinaire en Oncologie) study..J Clin Oncol2014;32:3520-6

[24] Ajani JA,Pisters PW,Mansfield PF,Charnsangavej C.CPT-11 plus cisplatin in patients with advanced, untreated gastric or gastroesophageal junction carcinoma: results of a phase II study..Cancer2002;94:641-6

[25] Dank M,Barone C,Yalcin S,Wenczl M,Cisar L,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 Oncol2008;19:1450-7

[26] Elimova E.Time-to-treatment failure as the primary end point of a first-line advanced gastric cancer randomized trial: how confused would you want us to be?.J Clin Oncol2015;33:2410

[27] Wils JA,Wagener DJ,Reis H,Conroy T,Leyvraz S.Sequential high-dose methotrexate and fluorouracil combined with doxorubicin--a step ahead in the treatment of advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group..J Clin Oncol1991;9:827-31

[28] MacDonald JS,Woolley PV,Ueno W,Smith F,Gisselbrecht C,Lagarde C.5-Fluorouracil, doxorubicin, and mitomycin (FAM) combination chemotherapy for advanced gastric cancer..Ann Intern Med1980;93:533-6

[29] Kelsen D,Saltz L,Ginn D,Heelan R,Vinciguerra V.FAMTX versus etoposide, doxorubicin, and cisplatin: a random assignment trial in gastric cancer..J Clin Oncol1992;10:541-8

[30] Webb A,Scarffe JH,Norman A,Hughes M,Findlay M,Oates J,Hickish T,Iveson T,Underhill C,Meehan M.Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer..J Clin Oncol1997;15:261-7

[31] Ajani JA.Standard chemotherapy for gastric carcinoma: is it a myth?.J Clin Oncol2000;18:4001-3

[32] Kim NK,Heo DS,Kim SY,Kang YK,Kim HT.A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer..Cancer1993;71:3813-8

[33] Al-Batran SE,Probst S,Hollerbach S,Rethwisch V,Homann N,Schuch G,Derigs HG,Grossmann J,Atmaca A,Knuth A.Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie..J Clin Oncol2008;26:1435-42

[34] Cunningham D,Rao S,Nicolson M,Middleton G,Oates J.Capecitabine and oxaliplatin for advanced esophagogastric cancer..N Engl J Med2008;358:36-46

[35] Ajani JA,Bodoky G,Lichinitser M,Vynnychenko I,Lang I.Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial..J Clin Oncol2010;28:1547-53

[36] Ajani JA,Lichinitser M,Bodoky G,Cascinu S,Zaucha R,Ferry D.Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study..Eur J Cancer2013;49:3616-24

[37] Koizumi W,Hara T,Akiya T,Miyashita K,Kobayashi O,Toh Y,Takagi S,Yanaoka K,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 Oncol2008;9:215-21

[38] Van Cutsem E,Tjulandin S,Constenla M,Rodrigues A,Chao Y,Risse ML.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 Oncol2006;24:4991-7

[39] Ajani JA,Tjulandin SA,Chao Y,Majlis A,Van Cutsem E.Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma..J Clin Oncol2005;23:5660-7

[40] Al-Batran SE,Hofheinz R,Rethwisch V,Stoehlmacher J,Mahlberg R,Seipelt G,Pauligk C,Jager E.Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie..Ann Oncol2008;19:1882-7

[41] Van Cutsem E,Tabernero J,Middleton G,Reichardt P,Cohn A,Clemens M,Moiseyenko V,Richards DA,Pernot S,Hitier S.Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study..Ann Oncol2015;26:149-56

[42] Shah MA,Stoller R,Kemeny M,Su YB,Capanu M,Ritch P,Kelsen DP.Randomized multicenter phase II study of modified docetaxel, cisplatin, and fluorouracil (DCF) versus DCF plus growth factor support in patients with metastatic gastric adenocarcinoma: a study of the US Gastric Cancer Consortium..J Clin Oncol2015;33:3874-9

[43] Fuchs CS,Yong CJ,Passalacqua R,Safran H,Aprile G,Melichar B,Topuzov E,Chau I,Sivanandan C,Koshiji M,Liepa AM,Schwartz JD.Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial..Lancet2014;383:31-9

[44] Wilke H,Van Cutsem E,Bodoky G,Hironaka S,Lipatov O,Cunningham D,Komatsu Y,Emig M,Ferry D,Schwartz JD.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 Oncol2014;15:1224-35

[45] Thuss-Patience PC,Bichev D,Hinke A,Dogan Y,Schumacher G.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 Cancer2011;47:2306-14

[46] Kang JH,Lim DH,Oh SY,Hwang IG,Nam E,Lee J,Park YS,Kang WK.Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone..J Clin Oncol2012;30:1513-8

[47] Hironaka S,Yasui H,Tsuda M,Sugimoto N,Tokunaga S,Esaki T,Fujitani K,Ura T,Morita S,Boku N.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 Oncol2013;31:4438-44

[48] Muro K,Shankaran V,Catenacci D,Eder JP,Le DT,McRee AJ,Pathiraja K,Emancipator K,Koshiji M.Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial..Lancet Oncol2016;17:717-26

[49] Chung HC,Wyrwicz L,Lee KW,Lee SS,Keilholz U,Plummer ER,Melichar B,Chin KM,Cuillerot JM,Safran H.Avelumab (MSB0010718C; anti-PD-L1) in patients with advanced gastric or gastroesophageal junction cancer from JAVELIN solid tumor phase Ib trial: analysis of safety and clinical activity..J Clin Oncol2016;34 Suppl 15:abstr4009

[50] Chung HC,Wyrwicz L,Lee KW,Chin KM,Kang YK.Safety, PD-L1 expression, and clinical activity of avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with advanced gastric or gastroesophageal junction cancer..J Clin Oncol2016;34 Suppl 4:abstr167

[51] Fuchs CS,Jang RWJ,Satoh T,Sun W,Shah MA,Garrido M,Mandala M,Catenacci DVT,Wang J,Dalal RP.KEYNOTE-059 cohort 1: efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer..J Clin Oncol2017;35 Suppl 15:abstr4003

[52] Janjigian YY,Calvo E,Ascierto PA,Peltola KJ,Evans TRJ,Chau I,Harbison CT,Bendell JC.Nivolumab ± ipilimumab in pts with advanced (adv)/metastatic chemotherapy-refractory (CTx-R) gastric (G), esophageal (E), or gastroesophageal junction (GEJ) cancer: CheckMate 032 study..J Clin Oncol2017;35 Suppl 15:abstr4014

[53] Bekaii-Saab T.Identifying and targeting cancer stem cells in the treatment of gastric cancer..Cancer2017;123:1303-12 PMCID:PMC5412889

[54] Cohen DJ,Kindler HL,Bekaii-Saab TB,Janjigian YY,Chan E,Urba S,Kozuch P,Vandris K,Hochster HS.Vismodegib (V), a hedgehog (HH) pathway inhibitor, combined with FOLFOX for first-line therapy of patients (pts) with advanced gastric and gastroesophageal junction (GEJ) carcinoma: a New York Cancer Consortium led phase II randomized study..J Clin Oncol2013;31 Suppl 15:abstr4011

[55] Sonbol MB.A clinical trial protocol paper discussing the BRIGHTER study..Future Oncol2018;

[56] Yoon C,Schmidt B,Lee HJ,Janjigian YY,Yoon SS.CD44 expression denotes a subpopulation of gastric cancer cells in which Hedgehog signaling promotes chemotherapy resistance..Clin Cancer Res2014;20:3974-88 PMCID:PMC4135312

[57] Chiappinelli KB,Desrichard A,Henke C,Hein A,Cope LM,Makarov V,Slamon DJ,Pardoll DM,Zahnow CA,Chan TA,Strick R.Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses..Cell2015;162:974-86 PMCID:PMC4556003

[58] Dong C,Temann UA,Allison JP,Flavell RA.ICOS co-stimulatory receptor is essential for T-cell activation and function..Nature2001;409:97-101

[59] Ajani JA,Almhanna K,Chao J,Denlinger CS,Farjah F,Gerdes H,Glasgow RE,Hochwald S,Ilson DH,Johung KL,Kleinberg LR,Leong S,Lockhart AC,Mulcahy MF,Perry KA,Scott WJ,Washington MK,Willett CG,Zelman D,Sundar H.Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology..J Natl Compr Canc Netw2016;14:1286-312

[60] Yonemura Y,Endou Y,Mizumoto A,Li Y,Takeshita K,Takao N,Sako S.Peritoneal cancer treatment..Expert Opin Pharmacother2014;15:623-36

[61] Badgwell B,Das P,Wang X,Fournier K,Mansfield P.Phase II trial of laparoscopic hyperthermic intraperitoneal chemoperfusion for peritoneal carcinomatosis or positive peritoneal cytology in patients with gastric adenocarcinoma..Ann Surg Oncol2017;24:3338-44