TumorDiagnostik & Therapie 2022; 43(02): 112-115
DOI: 10.1055/a-1688-7310
Übersicht
Schwerpunkt

„Licht am Ende des Tunnels“ – Zu aktuellen Therapien beim HER2 positiven Adenokarzinom des Magens und gastroösophagealen Übergangs

Alexander Stein
,
Mascha Binder

Trotz insgesamt rückläufiger Inzidenzen sind Adenokarzinome des Magens und des gastroösophagealen Übergangs weiterhin häufige Krebserkrankungen. Weltweit stellt diese Erkrankungsgruppe die dritt- bis vierthäufigste Krebstodesursache dar [1]. Diese Tumoren werden oft in einem fortgeschrittenen Stadium diagnostiziert, entweder als nicht resezierbare lokoregionäre oder als metastasierte Erkrankung. Die Prognose ist mit einer 5-Jahres-Überlebensrate von 5–20% ungünstig.



Publication History

Article published online:
02 March 2022

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  • Literatur

  • 1 Sung H, Ferlay J, Siegel RL. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021; 71: 209-249 DOI: 10.3322/caac.21660. (PMID: 33538338)
  • 2 Smyth EC, Verheij M, Allum W. et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27: v38-v49 DOI: 10.1093/annonc/mdw350. (PMID: 27664260)
  • 3 Shitara K, Doi T, Dvorkin M. 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 DOI: 10.1016/S1470-2045(18)30739-3. (PMID: 30355453)
  • 4 Fuchs CS, Tomasek J, Yong CJ. 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 2013; 383: 31-39 DOI: 10.1016/S0140-6736(13)61719-5. (PMID: 24094768)
  • 5 Wilke H, Muro K, Van Cutsem E. 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 DOI: 10.1016/S1470-2045(14)70420-6. (PMID: 25240821)
  • 6 Sun JM, Shen L, Shah MA. et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet 2021; 398: 759-771 DOI: 10.1016/S0140-6736(21)01234-4. (PMID: 34454674)
  • 7 Janjigian YY, Shitara K, Moehler M. 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 DOI: 10.1016/S0140-6736(21)00797-2. (PMID: 34102137)
  • 8 Ruschoff J, Dietel M, Baretton G. et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch 2010; 457: 299-307 DOI: 10.1007/s00428-010-0952-2. (PMID: 20665045)
  • 9 Bang Y, Chung H, Xu J. et al. Pathological features of advanced gastric cancer (GC): Relationship to human epidermal growth factor receptor 2 (HER2) positivity in the global screening programme of the ToGA trial. J Clin Oncol 2009; 27: 4556
  • 10 Bang YJ, Van Cutsem E, Feyereislova 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 DOI: 10.1016/S0140-6736(10)61121-X. (PMID: 20728210)
  • 11 Haffner I, Schierle K, Raimundez E. et al. HER2 Expression, Test Deviations, and Their Impact on Survival in Metastatic Gastric Cancer: Results From the Prospective Multicenter VARIANZ Study. J Clin Oncol 2021; 39: 1468-1478 DOI: 10.1200/JCO.20.02761. (PMID: 33764808)
  • 12 Hofheinz RD, Hegewisch-Becker S, Kunzmann V. et al. Trastuzumab in combination with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel as perioperative treatment for patients with human epidermal growth factor receptor 2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the Arbeitsgemeinschaft Internistische Onkologie Gastric Cancer Study Group. Int J Cancer 2021; 149: 1322-1331 DOI: 10.1002/ijc.33696. (PMID: 34019698)
  • 13 Hofheinz R, Haag GM, Ettrich T. Perioperative trastuzumab and pertuzumab in combination with FLOT versus FLOT alone for HER2-positive resectable esophagogastric adenocarcinoma: Final results of the PETRARCA multicenter randomized phase II trial of the AIO. J Clin Oncol 2020; 38.
  • 14 Wagner AD, Grabsch HI, Mauer M. et al. EORTC-1203-GITCG – the "INNOVATION"-trial: Effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab plus pertuzumab, in the perioperative treatment of HER2 positive, gastric and gastroesophageal junction adenocarcinoma on pathologic response rate: a randomized phase II-intergroup trial of the EORTC-Gastrointestinal Tract Cancer Group, Korean Cancer Study Group and Dutch Upper GI-Cancer group. BMC Cancer 2019; 19: 494 DOI: 10.1186/s12885-019-5675-4. (PMID: 31126258)
  • 15 Stein A, Paschold L, Tintelnot J. Ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in previously untreated HER2 positive locally advanced or metastastic esophagogastric adenocarcinoma (EGA): Results of the randomized phase II INTEGA trial (AIO STO 0217). Annals of Oncology 2021; 32 DOI: 10.1016/annonc/annonc741. (PMID: 32487035)
  • 16 Janjigian YY, Maron SB, Chatila WK. et al. First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial. Lancet Oncol 2020; 21: 821-831 DOI: 10.1016/S1470-2045(20)30169-8. (PMID: 32437664)
  • 17 Rha SY, Lee C, Kim H. A multi-institutional phase Ib/II trial of first-line triplet regimen (Pembrolizumab, Trastuzumab, Chemotherapy) for HER2-positive advanced gastric and gastroesophageal junction cancer (PANTHERA Trial): Molecular profiling and clinical update. J Clin Oncol 2021; 39: 218 DOI: 10.1200/JCO.20.01802. (PMID: 33555912)
  • 18 Hecht JR, Bang YJ, Qin SK. 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 2015; DOI: 10.1200/JCO.2015.62.6598. (PMID: 26628478)
  • 19 Tabernero J, Hoff PM, Shen L. 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: 1372-1384 DOI: 10.1016/S1470-2045(18)30481-9. (PMID: 30217672)
  • 20 Satoh T, Xu RH, Chung HC. 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: 2039-2049 DOI: 10.1200/JCO.2013.53.6136. (PMID: 24868024)
  • 21 Thuss-Patience PC, Shah MA, Ohtsu A. 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: 640-653 DOI: 10.1016/S1470-2045(17)30111-0. (PMID: 28343975)
  • 22 Janjigian YY, Kawazoe A, Yanez P. Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (G/GEJ) cancer: Initial findings of the global phase 3 KEYNOTE-811 study. J Clin Oncol 2021; 39: 4013 DOI: 10.1038/s41586-021-04161-3. (PMID: 34912120)
  • 23 Shitara K, Bang YJ, Iwasa S. et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med 2020; 382: 2419-2430 DOI: 10.1056/NEJMoa2004413. (PMID: 32469182)
  • 24 Van Cutsem E, Di Bartolomeo M, Smyth EC. Primary analysis of a phase II single-arm trial of trastuzumab deruxtecan (T-DXd) in western patients (Pts) with HER2-positive (HER2+) unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer who progressed on or after a trastuzumab-containing regimen. Annals of Oncology 2021; 32 DOI: 10.1016/annonc/annonc741. (PMID: 32339253)