Zusammenfassung
Das Pankreaskarzinom ist nach wie vor schwierig zu behandeln und hat trotz gewisser Fortschritte in den letzten Jahren, insbesondere der Etablierung verschiedener Kombinationschemotherapien, eine schlechte Prognose. Einen ausreichenden Allgemeinzustand vorausgesetzt, wird für alle Patienten eine Systemtherapie empfohlen. Nach kurativer Resektion kann die adjuvante Chemotherapie die mediane rezidivfreie Überlebenszeit signifikant verlängern sowie das 5‑Jahres-Überleben erhöhen. Im metastasierten Stadium soll die palliative Chemotherapie die Überlebenszeit und die Lebensqualität verbessern. Bei grenzwertig resektablen Tumoren verbessert eine kurzzeitige neoadjuvante Chemotherapie das Überleben, ohne notwendigerweise die Resektabilität zu beeinflussen. Bei lokal fortgeschrittenen Tumoren kann durch eine intensivere Chemotherapie bei manchen Patienten eine sekundäre Resektabilität erreicht werden. Im Gegensatz zu den meisten anderen Tumorerkrankungen gibt es noch keine feste Rolle für die Immuntherapie, neue Konzepte werden jedoch in Studien erprobt. Bei den zielgerichteten Therapien waren zuletzt Fortschritte zu verzeichnen, die aber aktuell nur den kleinen Teil der Patienten mit Keimbahn-BRCA-Mutationen, KRAS-Wildtyp oder der seltenen KRAS-G12C-Mutation betreffen. Weitere Fortschritte, z. B. für Patienten mit anderen KRAS-Mutationen, sind in den nächsten Jahren zu erwarten. Ein besseres Verständnis der molekularen Resistenzmechanismen des individuellen Patienten gegenüber der klassischen Chemotherapie, Immuntherapie und zielgerichteten Therapie ist für weitere relevante Fortschritte in der Systemtherapie dringend erforderlich.
Abstract
Pancreatic cancer is still difficult to treat, and despite some progress in recent years, especially the development of combination chemotherapy, the prognosis remains dismal. Chemotherapy is recommended for every patient that is fit enough: after curative resection, adjuvant chemotherapy can increase disease-free and 5‑year survival. In patients with metastases, palliative chemotherapy can improve survival and quality of life. In patients with borderline resectable tumors, short-course chemotherapy can improve survival without necessarily affecting resectability. In patients with locally advanced cancer, induction chemotherapy can result in secondary resectability. In contrast to most other types of cancer there is no role for immunotherapy yet, but new strategies are being investigated in clinical trials. There have been advances in targeted therapy, but these are limited to the few patients with BRCA germline mutations, KRAS wildtype or the rare KRAS G12C mutations. Further progress, for example, for patients with other KRAS mutations can be expected in the coming years. A better understanding of the molecular resistance mechanisms in the individual patient against chemotherapy, immunotherapy and targeted therapy will be necessary to further improve systemic therapy in the future.
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C. Springfeld hat an Advisory Boards von Astra Zeneca, Bayer, Incyte, MSD, Roche, Servier und Taiho teilgenommen. D. Jäger hat Honorare für Beratertätigkeiten oder Vorträge von CureVac, Definiens, Hoffmann-La Roche, Genmab, Life Science, VAXIMM, OncoOne Research & Development Research, Oncolytics Biotech, Zelluna, HDIT, AYOXXA, Seattle Genetics, BreakBio Corp., Roche Pharma, BMS, MSD, und Astra Zeneca erhalten sowie Unterstützung für Kongressteilnahmen von Amgen, Oryx, Roche Glycart, Parexel und BMS. S. Krug und J. Neoptolemos geben an, dass kein Interessenkonflikt besteht.
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Springfeld, C., Krug, S., Neoptolemos, J. et al. Aktuelle systemische Therapie beim Pankreaskarzinom. Onkologie 29, 769–777 (2023). https://doi.org/10.1007/s00761-023-01382-1
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DOI: https://doi.org/10.1007/s00761-023-01382-1