Medikamentöse Therapiestrategien des Magenkarzinoms

Magdalena Scheck; Sylvie Lorenzen

doi:10.1055/a-2539-0873

Onkologische Welt, Inhaltsverzeichnis

Onkologische Welt 2025; 16(06): 329-345
DOI: 10.1055/a-2539-0873

Übersicht

Medikamentöse Therapiestrategien des Magenkarzinoms

Authors

Magdalena Scheck
Sylvie Lorenzen

Abstract

Zusammenfassung

Magenkarzinome sind in Deutschland bei Frauen für 2,3 % und bei Männern für 3,5 % der Krebsneuerkrankungen verantwortlich und gehen mit einer hohen Letalitätsrate einher [1]. In der Therapie wird zwischen einer lokalen und einer metastasierten Tumorerkrankung unterschieden. Neue Behandlungsverfahren wie Immuntherapie und zielgerichtete Therapie halten in beiden Fällen Einzug in die derzeitigen Therapiestrategien und verbessern damit die Prognose der Patienten.

Volltext

Referenzen

Literatur
1 Ronckers C, Spix C, Trübenbach C. et al. Krebs in Deutschland für 2019/2020. 2023
2 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 A Cancer J Clin 2021; 71: 209-249
3 National Cancer Institute. SEER Cancer Statistics Review 1975–2016, Cancer of the Stomach (Invasive) [Internet]. Zugriff am 30. Mai 2025 unter: https://seer.cancer.gov/archive/csr/1975_2016/
4 Lordick F, Carneiro F, Cascinu S. et al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of Oncology 2022; 33: 1005-1020
5 Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014; 513: 202-209
6 Gertsen EC, Brenkman HJF, van Hillegersberg R. et al. ¹⁸ F-Fludeoxyglucose–Positron Emission Tomography/Computed Tomography and Laparoscopy for Staging of Locally Advanced Gastric Cancer: A Multicenter Prospective Dutch Cohort Study (PLASTIC). JAMA Surg 2021; 156: e215340
7 Moehler M, Al-Batran S-E, Andus T. et al. S3-Leitlinie Magenkarzinom – Diagnostik und Therapie der Adenokarzinome des Magens und des ösophagogastralen Übergangs – Langversion 2.0. Z Gastroenterol 2019; 57: 1517-1632
8 Cunningham D. Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer. N Engl J Med 2006; 355: 11-20
9 Al-Batran S-E, Hofheinz RD, Pauligk C. et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase ⅔ trial. Lancet Oncol 2016; 17: 1697-708
10 Al-Batran S-E, Homann N, Pauligk C. 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 ⅔ trial. Lancet 2019; 393: 1948-1957
11 Becker K, Mueller JD, Schulmacher C. et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy: Response of Gastric Carcinoma to Chemotherapy. Cancer 2003; 98: 1521-1530
12 Lordick F, Mauer ME, Stocker G. et al. Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN + and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study. Annals of Oncology 2025; 36: 197-207
13 Leong T, Smithers BM, Michael M. et al. Preoperative Chemoradiotherapy for Resectable Gastric Cancer. N Engl J Med 2024; 391: 1810-1821
14 Obermannová RL, Leong T. ESMO Clinical Practice Guideline interim update on the treatment of locally advanced oesophageal and oesophagogastric junction adenocarcinoma and metastatic squamous-cell carcinoma. ESMO Open 2025; 10: 104134
15 Hoeppner J, Brunner T, Schmoor C. et al. Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer N Engl. J Med 2025; 392: 323-335
16 The GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research International Collaboration) Group. Benefit of Adjuvant Chemotherapy for Resectable Gastric Cancer: A Meta-analysis. JAMA 2010; 303: 1729
17 Cats A, Jansen EPM, van Grieken NCT. 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
18 Lorenzen S, Götze TO, Thuss-Patience P. et al. Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial. J Clin Oncol 2024; 42: 410-420
19 Janjigian YY, Al-Batran S-E, Wainberg ZA. et al. LBA73 Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the global, phase III MATTERHORN study. Annals of Oncology 2023; 34: S1315-S1316
20 Janjigian YY, Al-Batran S-E, Wainberg ZA. et al. Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer. N Engl J Med 2025
21 Shitara K, Rha SY, Wyrwicz LS. et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. The Lancet Oncology 2024; 25: 212-224
22 Shitara K, Rha SY, Wyrwicz LS. et al. LBA3 Final analysis of the phase III KEYNOTE-585 study of pembrolizumab plus chemotherapy vs chemotherapy as perioperative therapy in locally-advanced gastric and gastroesophageal junction cancer. Annals of Oncology 2024; 35: S213
23 Al-Batran S-E, Lorenzen S, Thuss-Patience PC. et al. A randomized, open-label, phase II/III efficacy and safety study of atezolizumab in combination with FLOT versus FLOT alone in patients with gastric cancer and adenocarcinoma of the oesophagogastric junction and high immune responsiveness: The IKF-S633/DANTE trial, a trial of AIO in collaboration with SAKK. JCO 2023; 41: TPS4177-TPS4177
24 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. The Lancet 2021; 398: 27-40
25 André T, Tougeron D, Piessen G. et al. Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability-High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study. JCO 2022; JCO.22.00686
26 Raimondi A, Lonardi S, Murgioni S. et al. Tremelimumab and durvalumab as neoadjuvant or non-operative management strategy of patients with microsatellite instability-high resectable gastric or gastroesophageal junction adenocarcinoma: the INFINITY study by GONO. Annals of Oncology 2025; 36: 285-296
27 Pietrantonio F, Miceli R, Raimondi A. et al. Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer. J Clin Oncol 2019; 37: 3392-400
28 Hofheinz R, 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
29 Al-Batran S-E, Haag GM, Ettrich TJ. et al. 1421MO Final results and subgroup analysis of the PETRARCA randomized phase II AIO trial: Perioperative trastuzumab and pertuzumab in combination with FLOT versus FLOT alone for HER2 positive resectable esophagogastric adenocarcinoma. Annals of Oncology 2020; 31: S899
30 Wagner A, Grabsch H, Mauer M. et al. O-5 Integrating trastuzumab (T), with or without pertuzumab (P), into perioperative chemotherapy (CT) of HER-2 + gastric cancer (GC) – subgroup analyses of EORTC 1203 “INNOVATION”, a collaboration with KCSG and DUCG. Annals of Oncology 2023; 34: S182
31 Wagner AD, Grabsch HI, Mauer ME. et al. LBA331: EORTC-1203 GITC “INNOVATION”: Integration of trastuzumab (T), with or without pertuzumab (P), into perioperative chemotherapy of HER-2 positive stomach cancer: Overall survival results. ASCO GI 2025 2025 Jan
32 Glatz T, Verst R, Kuvendjiska J. et al. Pattern of Recurrence and Patient Survival after Perioperative Chemotherapy with 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) for Locally Advanced Esophagogastric Adenocarcinoma in Patients Treated Outside Clinical Trials. J Clin Med 2020; 9: 2654
33 Ajani JA, D’Amico TA, Bentrem DJ. et al. Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network 2022; 20: 167-192
34 Hall PS, Swinson D, Cairns DA. 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 Oncology 2021; 7: 869-877
35 Sama S, Nevala-Plagemann CD, Smith J. et al. Real-world outcomes with front-line doublet versus triplet chemotherapy in advanced gastroesophageal adenocarcinoma. JCO 2023; 41: 313-313
36 Zaanan A, Bouché O, de la Fouchardière C. et al. TFOX versus FOLFOX in first-line treatment of patients with advanced HER2-negative gastric or gastro-oesophageal junction adenocarcinoma (PRODIGE 51- FFCD-GASTFOX): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol 2025; S1470-2045 25)00130–5
37 Van Cutsem E, Moiseyenko VM, Tjulandin S. 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
38 Zaanan A, Bouche O, De La Fouchardiere C. et al. LBA77 5-fluorouracil and oxaliplatin with or without docetaxel in the first-line treatment of HER2 negative locally advanced (LA) unresectable or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma (GASTFOX-PRODIGE 51): A randomized phase III trial sponsored by the FFCD. Annals of Oncology 2023; 34: S1318
39 Van Cutsem E, Bang Y-J, Feng-Yi F. et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer 2015; 18: 476-484
40 Bang Y-J, 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
41 Porth I, Hirsch D, Ceribas Y. et al. Comprehensive biomarker analysis of long-term response to trastuzumab in patients with HER2-positive advanced gastric or gastroesophageal adenocarcinoma. Eur J Cancer 2023; 183: 119-130
42 Janjigian YY, Kawazoe A, Bai Y. et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. The Lancet 2023; 402: 2197-208
43 Janjigian YY, Kawazoe A, Bai Y. et al. 1400O Final overall survival for the phase III, KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for HER2 + advanced, unresectable or metastatic G/GEJ adenocarcinoma. Annals of Oncology 2024; 35: S877-S878
44 Janjigian YY, Rha S, Oh D. et al. SO-7 Co-occurring HER2 and PD-L1 expression in patients with HER2-positive trastuzumab-refractory gastric cancer (GC)/gastroesophageal junction adenocarcinoma (GEJA): Biomarker analysis from the trastuzumab deruxtecan (T-DXd) DESTINY-Gastric03 trial. Annals of Oncology 2022; 33: S358-S359
45 Shitara K, Bang Y-J, Iwasa S. et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med 2020; 382: 2419-2430
46 Van Cutsem E, Di Bartolomeo M, Smyth E. et al. Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study. The Lancet Oncology 2023; 24: 744-756
47 Lordick F, Al-Batran SE, Arnold D. et al. Onkopedia Leitlinie Magenkarzinom [Internet]. 01/2024 Zugriff am 30. Mai 2025 unter: https://www.onkopedia.com/de/onkopedia/guidelines/magenkarzinom/@@guideline/html/index.html
48 National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) Gastric Cancer Version 1.2025 [Internet]. NCCN. 03/2025 Report No.: Version 1.2025 Zugriff am 30. Mai 2025 unter: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1434
49 Janjigian YY, van Laarhoven HWM, Rha SY. et al. 1401O Trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (pts) with advanced/metastatic HER2-positive (HER2 +) esophageal, gastric or gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03 (DG-03). Annals of Oncology 2024; 35: S878
50 Shitara K, Moehler MH, Ajani JA. et al. Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1 L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 4 year (yr) follow-up of CheckMate 649. JCO 2024; 42: 306-306
51 Rha SY, Oh D-Y, Yañez P. et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. The Lancet Oncology 2023; 24: 1181-1195
52 Moehler MH, Kato K, Arkenau H-T. et al. Rationale 305: Phase 3 study of tislelizumab plus chemotherapy vs placebo plus chemotherapy as first-line treatment (1 L) of advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). JCO 2023; 41: 286-286
53 Xu R-H, Oh D-Y, Kato K. et al. LBA80 Tislelizumab (TIS) plus chemotherapy (Chemo) vs placebo (PBO) plus chemo as first-line (1 L) treatment of advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC): Final analysis results of the RATIONALE-305 study. Annals of Oncology 2023; 34: S1320-S1321
54 Leone AG, Mai AS, Fong KY. et al. Immune checkpoint inhibitors in advanced gastroesophageal adenocarcinoma: a series of patient-level meta-analyses in different programmed death-ligand 1 subgroups. ESMO Open 2024; 9: 103962
55 Muro K, Kawakami H, Kadowaki S. et al. 1513MO A phase II study of nivolumab plus low dose ipilimumab as first -line therapy in patients with advanced gastric or esophago-gastric junction MSI-H tumor: First results of the NO LIMIT study (WJOG13320G/CA209–7W7). Annals of Oncology 2023; 34: S852-S853
56 Shitara K, Van Cutsem E, Bang Y-J. et al. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol 2020; 6: 1571-80
57 ESMO. ESMO Gastric Cancer Living Guideline [Internet]. Ann Oncol 2022; 2024 Sep. Report No.: 33 (10) 1005-1020 Zugriff am 28. Juli 2025 unter: https://www.esmo.org/living-guidelines/esmo-gastric-cancer-living-guideline
58 Sahin U, Türeci Ö, Manikhas G. et al. FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma. Ann Oncol 2021; 32: 609-6019
59 Shitara K, Van Cutsem E, Lordick F. et al. Final overall survival results from phase 3 SPOTLIGHT study evaluating zolbetuximab + mFOLFOX6 as first-line (1 L) treatment for patients (pts) with claudin 18 isoform 2 (CLDN18.2) + , HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. JCO 2024; 42: 4036-4036
60 Shah MA, Shitara K, Ajani JA. et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med 2023; 29: 2133-2141
61 Shitara K, Shah MA, Lordick F. et al. Zolbetuximab in Gastric or Gastroesophageal Junction Adenocarcinoma. N Engl J Med 2024; 391: 1159-1162
62 Shitara K, Lordick F, Bang Y-J. et al. Zolbetuximab + mFOLFOX6 as first-line (1 L) treatment for patients (pts) withclaudin-18.2 + (CLDN18.2 +)/HER2− locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Primary results from phase 3 SPOTLIGHT study. JCO 2023; 41: LBA292-LBA292
63 Ajani JA, Lordick F, Bang Y-J. et al. 135MO Updated efficacy and safety results from phase III SPOTLIGHT study evaluating zolbetuximab + mFOLFOX6 as first-line (1 L) treatment for patients with claudin-18 isoform 2-positive (CLDN18.2 +), HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Annals of Oncology 2023; 34: S1524-S1525
64 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
65 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 2014; 383: 31-39
66 Lorenzen S, Thuss-Patience P, Pauligk C. et al. FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel – results from the phase II RAMIRIS Study of the German Gastric Cancer Study Group at AIO. Eur J Cancer 2022; 165: 48-57
67 Marabelle A, Le DT, Ascierto PA. et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol 2020; 38: 1-10
68 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
69 Pavlakis N, Shitara K, Sjoquist KM. et al. INTEGRATE IIa: A randomised, double-blind, phase III study of regorafenib versus placebo in refractory advanced gastro-oesophageal cancer (AGOC)—A study led by the Australasian Gastro-intestinal Trials Group (AGITG). JCO 2023; 41: LBA294-LBA294
70 Wainberg ZA, Enzinger PC, Kang Y-K. et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. The Lancet Oncology 2022; 23: 1430-1440
71 Al-Batran S-E, Lorenzen S, Riera J. et al. LBA 4001: Effect of chemotherapy/targeted therapy alone vs. chemotherapy/targeted therapy followed by radical surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction: The IKF-575/RENAISSANCE phase III trial. ASCO 2024 2024 Jun
72 Chevallay M, Wassmer C-H, Iranmanesh P. et al. Multimodal treatment in oligometastatic gastric cancer. World J Gastrointest Oncol 2022; 14: 434-449
73 Fujitani K, Yang H-K, Mizusawa J. 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. The Lancet Oncology 2016; 17: 309-318
74 Al-Batran S-E, Homann N, Pauligk C. et al. Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial. JAMA Oncol 2017; 3: 1237