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Locally Advanced Unresectable Gastroesophageal Junction Adenocarcinoma

MedGen UID:
1692972
•Concept ID:
C5206339
•
Neoplastic Process

Definition

Gastroesophageal junction adenocarcinoma that has spread from its original site of growth to nearby tissues or lymph nodes and is not amenable to surgical resection. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLocally Advanced Unresectable Gastroesophageal Junction Adenocarcinoma

Professional guidelines

PubMed

Updated German guideline on diagnosis and treatment of squamous cell carcinoma and adenocarcinoma of the esophagus.
Porschen R, Fischbach W, Gockel I, Hollerbach S, Hölscher A, Jansen PL, Miehlke S, Pech O, Stahl M, Vanhoefer U, Ebert MPA
United European Gastroenterol J 2024 Apr;12(3):399-411. Epub 2024 Jan 29 doi: 10.1002/ueg2.12523. PMID: 38284661Free PMC Article
Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.
Ajani JA, D'Amico TA, Bentrem DJ, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Farjah F, Gerdes H, Gibson M, Grierson P, Hofstetter WL, Ilson DH, Jalal S, Keswani RN, Kim S, Kleinberg LR, Klempner S, Lacy J, Licciardi F, Ly QP, Matkowskyj KA, McNamara M, Miller A, Mukherjee S, Mulcahy MF, Outlaw D, Perry KA, Pimiento J, Poultsides GA, Reznik S, Roses RE, Strong VE, Su S, Wang HL, Wiesner G, Willett CG, Yakoub D, Yoon H, McMillian NR, Pluchino LA
J Natl Compr Canc Netw 2023 Apr;21(4):393-422. doi: 10.6004/jnccn.2023.0019. PMID: 37015332
Targeted Treatment of Esophagogastric Cancer.
Kopp HG, Hofheinz RD
Oncol Res Treat 2016;39(12):788-794. Epub 2016 Nov 22 doi: 10.1159/000452877. PMID: 27889780

Recent clinical studies

Etiology

Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: a meta-analysis of randomized clinical trials.
de Moraes FCA, Pasqualotto E, Chavez MP, Ferreira ROM, De Castria TB, Burbano RMR
BMC Cancer 2024 Feb 21;24(1):240. doi: 10.1186/s12885-024-11980-w. PMID: 38383390Free PMC Article
Global Ring Study to Investigate the Comparability of Total Assay Performance of Commercial Claudin 18 Antibodies for Evaluation in Gastric Cancer.
Jasani B, Taniere P, Schildhaus HU, Blighe K, Parry S, Wilkinson D, Atkey N, Clare-Antony S, McCabe C, Quinn C; CLDN Study Group, Dodson A
Lab Invest 2024 Jan;104(1):100284. Epub 2023 Nov 8 doi: 10.1016/j.labinv.2023.100284. PMID: 37949357
Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial.
Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, Van Cutsem E, Xu RH, Aprile G, Xu J, Chao J, Pazo-Cid R, Kang YK, Yang J, Moran D, Bhattacharya P, Arozullah A, Park JW, Oh M, Ajani JA
Lancet 2023 May 20;401(10389):1655-1668. Epub 2023 Apr 15 doi: 10.1016/S0140-6736(23)00620-7. PMID: 37068504
Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial.
Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, Qin Y, Qin S, Yin X, Liu B, Ba Y, Yang N, Voon PJ, Tanasanvimon S, Zhou C, Zhang WL, Shen L
Lancet Gastroenterol Hepatol 2021 Dec;6(12):1015-1024. Epub 2021 Oct 7 doi: 10.1016/S2468-1253(21)00313-7. PMID: 34626550
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.
Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK
Lancet Oncol 2017 May;18(5):640-653. Epub 2017 Mar 23 doi: 10.1016/S1470-2045(17)30111-0. PMID: 28343975

Diagnosis

Global Ring Study to Investigate the Comparability of Total Assay Performance of Commercial Claudin 18 Antibodies for Evaluation in Gastric Cancer.
Jasani B, Taniere P, Schildhaus HU, Blighe K, Parry S, Wilkinson D, Atkey N, Clare-Antony S, McCabe C, Quinn C; CLDN Study Group, Dodson A
Lab Invest 2024 Jan;104(1):100284. Epub 2023 Nov 8 doi: 10.1016/j.labinv.2023.100284. PMID: 37949357
Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial.
Xu J, Jiang H, Pan Y, Gu K, Cang S, Han L, Shu Y, Li J, Zhao J, Pan H, Luo S, Qin Y, Guo Q, Bai Y, Ling Y, Yang J, Yan Z, Yang L, Tang Y, He Y, Zhang L, Liang X, Niu Z, Zhang J, Mao Y, Guo Y, Peng B, Li Z, Liu Y, Wang Y, Zhou H; ORIENT-16 Investigators
JAMA 2023 Dec 5;330(21):2064-2074. doi: 10.1001/jama.2023.19918. PMID: 38051328Free PMC Article
Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.
Ajani JA, D'Amico TA, Bentrem DJ, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Farjah F, Gerdes H, Gibson M, Grierson P, Hofstetter WL, Ilson DH, Jalal S, Keswani RN, Kim S, Kleinberg LR, Klempner S, Lacy J, Licciardi F, Ly QP, Matkowskyj KA, McNamara M, Miller A, Mukherjee S, Mulcahy MF, Outlaw D, Perry KA, Pimiento J, Poultsides GA, Reznik S, Roses RE, Strong VE, Su S, Wang HL, Wiesner G, Willett CG, Yakoub D, Yoon H, McMillian NR, Pluchino LA
J Natl Compr Canc Netw 2023 Apr;21(4):393-422. doi: 10.6004/jnccn.2023.0019. PMID: 37015332
Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial.
Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, Qin Y, Qin S, Yin X, Liu B, Ba Y, Yang N, Voon PJ, Tanasanvimon S, Zhou C, Zhang WL, Shen L
Lancet Gastroenterol Hepatol 2021 Dec;6(12):1015-1024. Epub 2021 Oct 7 doi: 10.1016/S2468-1253(21)00313-7. PMID: 34626550
KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma.
Shah MA, Bennouna J, Doi T, Shen L, Kato K, Adenis A, Mamon HJ, Moehler M, Fu X, Cho BC, Bordia S, Bhagia P, Shih CS, Desai A, Enzinger P
Future Oncol 2021 Apr;17(10):1143-1153. Epub 2021 Feb 3 doi: 10.2217/fon-2020-0969. PMID: 33533655Free PMC Article

Therapy

Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial.
Qiu MZ, Oh DY, Kato K, Arkenau T, Tabernero J, Correa MC, Zimina AV, Bai Y, Shi J, Lee KW, Wang J, Poddubskaya E, Pan H, Rha SY, Zhang R, Hirano H, Spigel D, Yamaguchi K, Chao Y, Wyrwicz L, Disel U, Cid RP, Fornaro L, Evesque L, Wang H, Xu Y, Li J, Sheng T, Yang S, Li L, Moehler M, Xu RH; RATIONALE-305 Investigators
BMJ 2024 May 28;385:e078876. doi: 10.1136/bmj-2023-078876. PMID: 38806195
Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial.
Xu J, Jiang H, Pan Y, Gu K, Cang S, Han L, Shu Y, Li J, Zhao J, Pan H, Luo S, Qin Y, Guo Q, Bai Y, Ling Y, Yang J, Yan Z, Yang L, Tang Y, He Y, Zhang L, Liang X, Niu Z, Zhang J, Mao Y, Guo Y, Peng B, Li Z, Liu Y, Wang Y, Zhou H; ORIENT-16 Investigators
JAMA 2023 Dec 5;330(21):2064-2074. doi: 10.1001/jama.2023.19918. PMID: 38051328Free PMC Article
Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial.
Shah MA, Shitara K, Ajani JA, Bang YJ, Enzinger P, Ilson D, Lordick F, Van Cutsem E, Gallego Plazas J, Huang J, Shen L, Oh SC, Sunpaweravong P, Soo Hoo HF, Turk HM, Oh M, Park JW, Moran D, Bhattacharya P, Arozullah A, Xu RH
Nat Med 2023 Aug;29(8):2133-2141. Epub 2023 Jul 31 doi: 10.1038/s41591-023-02465-7. PMID: 37524953Free PMC Article
Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial.
Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, Van Cutsem E, Xu RH, Aprile G, Xu J, Chao J, Pazo-Cid R, Kang YK, Yang J, Moran D, Bhattacharya P, Arozullah A, Park JW, Oh M, Ajani JA
Lancet 2023 May 20;401(10389):1655-1668. Epub 2023 Apr 15 doi: 10.1016/S0140-6736(23)00620-7. PMID: 37068504
KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma.
Shah MA, Bennouna J, Doi T, Shen L, Kato K, Adenis A, Mamon HJ, Moehler M, Fu X, Cho BC, Bordia S, Bhagia P, Shih CS, Desai A, Enzinger P
Future Oncol 2021 Apr;17(10):1143-1153. Epub 2021 Feb 3 doi: 10.2217/fon-2020-0969. PMID: 33533655Free PMC Article

Prognosis

Updated German guideline on diagnosis and treatment of squamous cell carcinoma and adenocarcinoma of the esophagus.
Porschen R, Fischbach W, Gockel I, Hollerbach S, Hölscher A, Jansen PL, Miehlke S, Pech O, Stahl M, Vanhoefer U, Ebert MPA
United European Gastroenterol J 2024 Apr;12(3):399-411. Epub 2024 Jan 29 doi: 10.1002/ueg2.12523. PMID: 38284661Free PMC Article
Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.
Ajani JA, D'Amico TA, Bentrem DJ, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Farjah F, Gerdes H, Gibson M, Grierson P, Hofstetter WL, Ilson DH, Jalal S, Keswani RN, Kim S, Kleinberg LR, Klempner S, Lacy J, Licciardi F, Ly QP, Matkowskyj KA, McNamara M, Miller A, Mukherjee S, Mulcahy MF, Outlaw D, Perry KA, Pimiento J, Poultsides GA, Reznik S, Roses RE, Strong VE, Su S, Wang HL, Wiesner G, Willett CG, Yakoub D, Yoon H, McMillian NR, Pluchino LA
J Natl Compr Canc Netw 2023 Apr;21(4):393-422. doi: 10.6004/jnccn.2023.0019. PMID: 37015332
Distant Oncologic Outcome of Patients with Locally Advanced Unresectable and Metastatic Esophageal Cancer after Multimodality Treatment.
Anghel R, Constantinoiu S, Bacinschi X, Gales L, Toma RV, Trifanescu O
Chirurgia (Bucur) 2018 Jan-Feb;113(1):116-122. doi: 10.21614/chirurgia.113.1.116. PMID: 29509538
A Phase I/II Study of Docetaxel, Oxaliplatin, and Fluorouracil (D-FOX) Chemotherapy in Patients With Untreated Locally Unresectable or Metastatic Adenocarcinoma of the Stomach and Gastroesophageal Junction.
Blum Murphy MA, Qiao W, Mewada N, Wadhwa R, Elimova E, Takashi T, Ho L, Phan A, Baker J, Ajani J
Am J Clin Oncol 2018 Apr;41(4):321-325. doi: 10.1097/COC.0000000000000271. PMID: 26908161
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.
Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK
Lancet Oncol 2017 May;18(5):640-653. Epub 2017 Mar 23 doi: 10.1016/S1470-2045(17)30111-0. PMID: 28343975

Clinical prediction guides

Health-related quality of life in patients with CLDN18.2-positive, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: results from the SPOTLIGHT and GLOW clinical trials.
Lordick F, Van Cutsem E, Shitara K, Xu RH, Ajani JA, Shah MA, Oh M, Ganguli A, Chang L, Rhoten S, Bhattacharya P, Matsangou M, Park JW, Pophale R, Ranganath R, Kang YK
ESMO Open 2024 Aug;9(8):103663. Epub 2024 Aug 14 doi: 10.1016/j.esmoop.2024.103663. PMID: 39146670Free PMC Article
Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial.
Qiu MZ, Oh DY, Kato K, Arkenau T, Tabernero J, Correa MC, Zimina AV, Bai Y, Shi J, Lee KW, Wang J, Poddubskaya E, Pan H, Rha SY, Zhang R, Hirano H, Spigel D, Yamaguchi K, Chao Y, Wyrwicz L, Disel U, Cid RP, Fornaro L, Evesque L, Wang H, Xu Y, Li J, Sheng T, Yang S, Li L, Moehler M, Xu RH; RATIONALE-305 Investigators
BMJ 2024 May 28;385:e078876. doi: 10.1136/bmj-2023-078876. PMID: 38806195
Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial.
Xu J, Jiang H, Pan Y, Gu K, Cang S, Han L, Shu Y, Li J, Zhao J, Pan H, Luo S, Qin Y, Guo Q, Bai Y, Ling Y, Yang J, Yan Z, Yang L, Tang Y, He Y, Zhang L, Liang X, Niu Z, Zhang J, Mao Y, Guo Y, Peng B, Li Z, Liu Y, Wang Y, Zhou H; ORIENT-16 Investigators
JAMA 2023 Dec 5;330(21):2064-2074. doi: 10.1001/jama.2023.19918. PMID: 38051328Free PMC Article
Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial.
Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, Van Cutsem E, Xu RH, Aprile G, Xu J, Chao J, Pazo-Cid R, Kang YK, Yang J, Moran D, Bhattacharya P, Arozullah A, Park JW, Oh M, Ajani JA
Lancet 2023 May 20;401(10389):1655-1668. Epub 2023 Apr 15 doi: 10.1016/S0140-6736(23)00620-7. PMID: 37068504
Pembrolizumab or pembrolizumab plus chemotherapy versus standard of care chemotherapy in patients with advanced gastric or gastroesophageal junction adenocarcinoma: Asian subgroup analysis of KEYNOTE-062.
Satake H, Lee KW, Chung HC, Lee J, Yamaguchi K, Chen JS, Yoshikawa T, Amagai K, Yeh KH, Goto M, Chao Y, Lam KO, Han SR, Shiratori S, Shah S, Shitara K
Jpn J Clin Oncol 2023 Mar 7;53(3):221-229. doi: 10.1093/jjco/hyac188. PMID: 36533429Free PMC Article

Recent systematic reviews

Perioperative immune checkpoint inhibitors combined with chemotherapy versus chemotherapy for locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis of randomized controlled trials.
Huang D, Sun F, Ke L, Li S
Int Immunopharmacol 2024 Sep 10;138:112576. Epub 2024 Jun 27 doi: 10.1016/j.intimp.2024.112576. PMID: 38941672
Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: a meta-analysis of randomized clinical trials.
de Moraes FCA, Pasqualotto E, Chavez MP, Ferreira ROM, De Castria TB, Burbano RMR
BMC Cancer 2024 Feb 21;24(1):240. doi: 10.1186/s12885-024-11980-w. PMID: 38383390Free PMC Article
Overview of different available chemotherapy regimens combined with radiotherapy for the neoadjuvant and definitive treatment of esophageal cancer.
Tomasello G, Ghidini M, Barni S, Passalacqua R, Petrelli F
Expert Rev Clin Pharmacol 2017 Jun;10(6):649-660. Epub 2017 Apr 10 doi: 10.1080/17512433.2017.1313112. PMID: 28349718

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