Was ist neu beim Magenkarzinom? (2024)

Was ist neu?

Therapie des lokal fortgeschrittenen Adenokarzinoms des Magens und AEG Im lokal fortgeschrittenen Stadium werden multimodale Therapien wie die perioperative Chemotherapie mit FLOT oder die neoadjuvante Radiochemotherapie in nationalen und internationalen Leitlinien empfohlen. Die Integration der Immuntherapie in diese Konzepte hat das Potenzial, die Prognose wesentlich zu verbessern. Phase-II/III-Studien wie die DANTE-, die KEYNOTE-585- und die MATTERHORN-Studie zeigen ermutigende Ergebnisse hinsichtlich verbesserter pathologischer Remissionen, jedoch sind Daten zur Überlebenszeitverlängerung für unselektionierte Patienten bislang ernüchternd.

Neuartige Behandlungskonzepte für die palliative Therapie In der palliativen Therapie des metastasierten Magenkarzinoms bieten Immuntherapien und neue zielgerichtete Antikörpertherapien Hoffnung. Studien wie CheckMate-649 und KEYNOTE-859 zeigen eine Verbesserung des Überlebens und der Ansprechraten. Aktuell bestehen sowohl für Pembrolizumab als auch Nivolumab Zulassungen in der Erstlinienbehandlung von Tumoren mit positiver PD-L1-Expression. Bei HER2-positiven Tumoren konnte in der KEYNOTE-811-Studie gezeigt werden, dass Patienten von Kombinationstherapien mit Immuncheckpoint-Inhibition und anti-HER2-Therapien profitieren. Das Antikörper-Wirkstoff-Konjugat Trastuzumab-Deruxtecan ist eine vielversprechende Zweitlinien-Therapieoption für HER2-positive Tumore nach Therapieversagen mit Trastuzumab. Darüber hinaus zeigt der bispezifische Antikörper Zanidatamab vielversprechende Ergebnisse in der Erstlinienbehandlung. Neue zielgerichtete Therapien gegen CLDN18.2 und FGFR2b zeigen vielversprechende Daten. Der gegen Claudin 18.2 (CLDN18.2) gerichtete Antikörper Zolbetuximab führt bei Patienten mit CLDN18.2-positiver Erkrankung in der Erstlinientherapie zu einer Verbesserung des Überlebens, im Vergleich zu Chemotherapie allein, sodass eine Zulassung 2024 erwartet wird.

Abstract

In the locally advanced stage, multimodal therapies such as perioperative chemotherapy with FLOT or neoadjuvant radiochemotherapy are recommended. The integration of immunotherapy into these concepts could improve the prognosis. Phase II/III trials such as DANTE, KEYNOTE-585 and MATTERHORN show promising results in terms of pathological remissions but data on survival time extension for unselected patients are so far sobering. Immunotherapies and new targeted therapies offer hope in the palliative treatment of metastatic gastric cancer. Studies such as CheckMate-649 and KEYNOTE-859 show an improvement in survival and response rates. Currently, both pembrolizumab and nivolumab have been approved for the first-line treatment of tumors with positive PD-L1 expression. In HER2-positive tumors, the KEYNOTE-811 study showed that patients benefit from combination therapies with immune checkpoint inhibition and anti-HER2 therapies. The antibody-drug conjugate trastuzumab-deruxtecan is a promising second-line treatment option for HER2-positive tumors after treatment failure with trastuzumab.

In addition, the bispecific antibody zanidatamab shows promising results in first-line treatment. New targeted therapies against CLDN18.2 and FGFR2b are showing promising results. The anti-claudin 18.2 (CLDN18.2) antibody zolbetuximab leads to improved survival compared to chemotherapy alone in patients with CLDN18.2 positive disease in first-line therapy, with approval expected in 2024.

Publikationsverlauf

Artikel online veröffentlicht:
15. August 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• Literatur

• 1 Moehler M, Al-Batran SE, Andus T. et al. S3-Leitlinie Magenkarzinom – Diagnostik und Therapie der Adenokarzinome des Magens und des ösophagogastralen Übergangs – Langversion 2.0 – August 2019. AWMF-Registernummer: 032/009OL. Z Gastroenterol 2019; 57 (12) 1517-1632 DOI: 10.1055/a-1018-2516.

  Artikel in Thieme ConnectPubMedGoogle Scholar

• 2 Obermannová R, Alsina M, Cervantes A. et al. Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2022; 33 (10) 992-1004 DOI: 10.1016/j.annonc.2022.07.003. (PMID: 35914638)

  CrossrefPubMedGoogle Scholar

• 3 Lordick F, Carneiro F, Cascinu S. et al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2022; 33: 1005-1020 DOI: 10.1016/j.annonc.2022.07.004. (PMID: 35914639)

  CrossrefPubMedGoogle Scholar

• 4 Reynolds JV, Preston SR, O’Neill B. et al. Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial. Lancet Gastroenterol Hepatol 2023; 8 (11) 1015-1027 DOI: 10.1016/S2468-1253(23)00243-1. (PMID: 37734399)

  CrossrefPubMedGoogle Scholar

• 5 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 2023; 42 (04) 410-420 DOI: 10.1200/JCO.23.00975.

  CrossrefPubMedGoogle Scholar

• 6 sh*tara K, Rha SY, Wyrwicz LS. et al. LBA74 Pembrolizumab plus chemotherapy vs chemotherapy as neoadjuvant and adjuvant therapy in locally-advanced gastric and gastroesophageal junction cancer: the phase 3 KEYNOTE-585 study. Ann Oncol 2023; 34 (02) S1316 DOI: 10.1016/j.annonc.2023.10.075.

  CrossrefPubMedGoogle Scholar

• 7 Oh DY, Janjigian YY, Al-Batran SE. et al. 129O 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. Ann Oncol 2023; 34 (04) S1520-S1521 DOI: 10.1016/j.annonc.2023.10.265.

  CrossrefPubMedGoogle Scholar

• 8 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. J Clin Oncol 2023; 41 (02) 255-265 DOI: 10.1200/JCO.22.00686. (PMID: 35969830)

  CrossrefPubMedGoogle Scholar

• 9 Raimondi A, Palermo F, Prisciandaro M. et al. TremelImumab and Durvalumab Combination for the Non-OperatIve Management (NOM) of Microsatellite InstabiliTY (MSI)-High Resectable Gastric or Gastroesophageal Junction Cancer: The Multicentre, Single-Arm, Multi-Cohort, Phase II INFINITY Study. Cancers (Basel) 2021; 13 (11) 2839 DOI: 10.3390/cancers13112839. (PMID: 34200267)

  CrossrefPubMedGoogle Scholar

• 10 Janjigian YY, sh*tara 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)

  CrossrefPubMedGoogle Scholar

• 11 sh*tara K, Moehler M, Ajani J. et al. Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 4 year (yr) follow-up of CheckMate 649. J Clin Oncol 2024; 42 (03) 306 DOI: 10.1200/JCO.2024.42.3_suppl.3.

  CrossrefPubMedGoogle Scholar

• 12 Rha SY, Oh DY, 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. Lancet Oncol 2023; 24 (11) 1181-1195 DOI: 10.1016/S1470-2045(23)00515-6.

  CrossrefPubMedGoogle Scholar

• 13 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 DOI: 10.1016/S0140-6736(10)61121-X.

  CrossrefPubMedGoogle Scholar

• 14 Janjigian YY, Kawazoe A, Yañez P. et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature 2021; 600: 727-730 DOI: 10.1038/s41586-021-04161-3. (PMID: 34912120)

  CrossrefPubMedGoogle Scholar

• 15 Janjigian Y, 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 DOI: 10.1016/j.annonc.2022.04.406.

  CrossrefPubMedGoogle Scholar

• 16 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)

  CrossrefPubMedGoogle Scholar

• 17 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. The Lancet Oncology 2018; 19: 1372-1384 DOI: 10.1016/S1470-2045(18)30481-9. (PMID: 30217672)

  CrossrefPubMedGoogle Scholar

• 18 sh*tara K, Bang YJ, Iwasa S. et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med 2020; 382 (25) 2419-2430 DOI: 10.1056/NEJMoa2004413. (PMID: 32469182)

  CrossrefPubMedGoogle Scholar

• 19 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. Lancet Oncol 2023; 24 (07) 744-756 DOI: 10.1016/S1470-2045(23)00215-2. (PMID: 37068504)

  CrossrefPubMedGoogle Scholar

• 20 Rha SY, Chung HC. Breakthroughs in the Systemic Treatment of HER2-Positive Advanced/Metastatic Gastric Cancer: From Singlet Chemotherapy to Triple Combination. J Gastric Cancer 2023; 23 (01) 224-249 DOI: 10.5230/jgc.2023.23.e6. (PMID: 36751001)

  CrossrefPubMedGoogle Scholar

• 21 Ku G, Elimova E, Denlinger CS. et al. 1380P Phase (Ph) II Study of Zanidatamab + Chemotherapy (Chemo) in First-Line (1L) HER2 Expressing Gastroesophageal Adenocarcinoma (GEA). Ann Oncol 2021; 32 (05) S1044-S1045 DOI: 10.1016/j.annonc.2021.08.1489.

  CrossrefPubMedGoogle Scholar

• 22 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 (05) 609-619 DOI: 10.1016/j.annonc.2021.02.005. (PMID: 33610734)

  CrossrefPubMedGoogle Scholar

• 23 sh*tara K, Lordick F, Bang YJ. et al. 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. Lancet 2023; 401: 1655-1668 DOI: 10.1016/S0140-6736(23)00620-7. (PMID: 37068504)

  CrossrefPubMedGoogle Scholar

• 24 Shah MA, sh*tara 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 (08) 2133-2141 DOI: 10.1038/s41591-023-02465-7. (PMID: 37524953)

  CrossrefPubMedGoogle Scholar

• 25 Wainberg ZA, Enzinger PC, Kang YK. et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol 2022; 23 (11) 1430-1440 DOI: 10.1016/S1470-2045(22)00603-9. (PMID: 36244398)

  CrossrefPubMedGoogle Scholar