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Medikamentöse Therapie des Pankreaskarzinoms

Immer noch eine Domäne der Chemotherapie?

Medicinal treatment of pancreatic cancer

Still a domain of chemotherapy?

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Zusammenfassung

Hintergrund

Pankreaskarzinome gehören zu den tödlichsten aller bekannten Erkrankungen beim Menschen. Neue Therapieansätze werden dringend benötigt.

Ziel der Übersicht

Der Beitrag gibt eine kurze Übersicht über aktuell verfügbare Systemtherapieoptionen mit Fokus auf neuen Entwicklungen der letzten Jahre. Zudem werden mögliche zukünftige Trends beschrieben.

Datenlage

Obwohl die systemische Behandlung von Pankreaskarzinomen weiterhin schwierig ist, waren in den letzten Jahren deutliche Verbesserungen durch zytostatische Chemotherapien in der palliativen und insbesondere auch adjuvanten Situation zu verzeichnen. Während immuntherapeutische Ansätze gegenwärtig noch selektierten Einzelfällen vorbehalten sind, ist ein zunehmender Stellenwert der systematischen molekulargenetischen Charakterisierung und zielgerichteten individualisierten Therapieansätze zu beobachten.

Schlussfolgerung

Gegenwärtig bleibt die Behandlung von Patienten mit Pankreaskarzinom im Wesentlichen eine Domäne der Chemotherapie, aber es zeichnen sich neue Ansätze ab, die eine Revolutionierung der Therapielandschaft des Pankreaskarzinoms in der nahen Zukunft bewirken könnten.

Abstract

Background

Pancreatic cancer is among the most fatal of all known human malignancies and novel therapeutic concepts are urgently required.

Objectives

A brief overview of currently available options for systemic therapy is provided with a focus on new developments in recent years. In addition, an outlook on possible relevant trends for future advancements is given.

Data situation

Although the systemic treatment of pancreatic cancer remains challenging, in recent years significant progress has been made in cytostatic chemotherapy in palliative as well as adjuvant settings. While immunotherapeutic approaches currently remain restricted to selected individual cases, the systemic molecular genetic characterization and individualized targeted therapeutic approaches are increasingly gaining in importance.

Conclusion

Treatment of pancreatic cancer patients currently remains a domain of cytostatic chemotherapy but novel approaches are emerging that have the potential to revolutionize the therapeutic landscape of pancreatic cancer in the near future.

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Literatur

  1. 1.

    Ansari D, Ohlsson H, Althini C et al (2019) The hippo signaling pathway in pancreatic cancer. Anticancer Res 39:3317–3321

  2. 2.

    Beatty GL, O’hara MH, Lacey SF et al (2018) Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology 155:29–32

  3. 3.

    Bisht S, Brossart P, Feldmann G (2018) Current therapeutic options for pancreatic ductal adenocarcinoma. Oncol Res Treat 41:590–594

  4. 4.

    Bisht S, Brossart P, Maitra A et al (2010) Agents targeting the hedgehog pathway for pancreatic cancer treatment. Curr Opin Investig Drugs 11:1387–1398

  5. 5.

    Bisht S, Feldmann G (2018) Novel targets in pancreatic cancer therapy—current status and ongoing translational efforts. Oncol Res Treat 41:596–602

  6. 6.

    Blando J, Sharma A, Higa MG et al (2019) Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer. Proc Natl Acad Sci U S A 116:1692–1697

  7. 7.

    Bonds M, Rocha FG (2019) Contemporary review of borderline resectable pancreatic ductal adenocarcinoma. J Clin Med 8:1205

  8. 8.

    Burris HA 3rd, Moore MJ, Andersen J et al (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15:2403–2413

  9. 9.

    Cancer Genome Atlas Research Network, Electronic Address AaDHE, Cancer Genome Atlas Research N (2017) Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell 32(e113):185–203e13

  10. 10.

    Canon J, Rex K, Saiki AY et al (2019) The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature 575:217–223

  11. 11.

    Conroy T, Desseigne F, Ychou M et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825

  12. 12.

    Conroy T, Hammel P, Hebbar M et al (2018) FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med 379:2395–2406

  13. 13.

    Hyman DM, van Tilburg CM, Albert CM, Tan DSW, Geoerger B, Farago AF, Laetsch TW, Kummar S, Doz F, Lassen UN, Dubois SG, Mcdermott R, Mascarenhas L, Berlin JD, Rudzinski ER, Cox MC, Nanda S, Childs BH, Drilon A, Hong DS (2019) Durability of response with larotrectinib in adult and pediatric patients with TRK fusion cancer. Ann Oncol 30(suppl_5):v159–v193. https://doi.org/10.1093/annonc/mdz244

  14. 14.

    Di Magliano MP, Logsdon CD (2013) Roles for KRAS in pancreatic tumor development and progression. Gastroenterology 144:1220–1229

  15. 15.

    Doherty GJ, Tempero M, Corrie PG (2018) HALO-109-301: a Phase III trial of PEGPH20 (with gemcitabine and nab-paclitaxel) in hyaluronic acid-high stage IV pancreatic cancer. Future Oncol 14:13–22

  16. 16.

    Fakih M, O’neil B, Price TJ et al (2019) Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12C inhibitor, in advanced solid tumors. J Clin Oncol 37:3003–3003

  17. 17.

    Feldmann G, Beaty R, Hruban RH et al (2007) Molecular genetics of pancreatic intraepithelial neoplasia. J Hepatobiliary Pancreat Surg 14:224–232

  18. 18.

    Golan T, Hammel P, Reni M et al (2019) Maintenance olaparib for Germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med 381:317–327

  19. 19.

    Hammel P, Fabienne P, Mineur L et al (2020) Erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial. Eur J Cancer 124:91–101

  20. 20.

    Hidalgo M, Cascinu S, Kleeff J et al (2015) Addressing the challenges of pancreatic cancer: future directions for improving outcomes. Pancreatology 15:8–18

  21. 21.

    Hingorani SR, Zheng L, Bullock AJ et al (2018) HALO 202: randomized phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine versus nab-paclitaxel/gemcitabine in patients with untreated, metastatic pancreatic ductal adenocarcinoma. J Clin Oncol 36:359–366

  22. 22.

    Kindler HL, Hammel P, Reni M et al (2019) Olaparib as maintenance treatment following first-line platinum-based chemotherapy (PBC) in patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC): Phase III POLO trial. J Clin Oncol 37:LBA4

  23. 23.

    Le DT, Durham JN, Smith KN et al (2017) Mismatch repair deficiency predicts response of solid tumors to PD‑1 blockade. Science 357:409–413

  24. 24.

    Lowery MA, Jordan EJ, Basturk O et al (2017) Real-time genomic profiling of pancreatic ductal adenocarcinoma: potential actionability and correlation with clinical phenotype. Clin Cancer Res 23:6094–6100

  25. 25.

    Macarulla T, Pazo-Cid R, Guillen-Ponce C et al (2019) Phase I/II trial to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel in combination with gemcitabine in patients with pancreatic cancer and an ECOG performance status of 2. J Clin Oncol 37:230–238

  26. 26.

    Maitra A, Hruban RH (2008) Pancreatic cancer. Annu Rev Pathol 3:157–188

  27. 27.

    Moore MJ, Goldstein D, Hamm J et al (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25:1960–1966

  28. 28.

    Mullard A (2019) Cracking KRAS. Nat Rev Drug Discov 18:887–891

  29. 29.

    Neoptolemos JP, Palmer DH, Ghaneh P et al (2017) Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet 389:1011–1024

  30. 30.

    O’reilly EM, Hechtman JF (2019) Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion. Ann Oncol 30:viii36–viii40

  31. 31.

    Oettle H, Neuhaus P, Hochhaus A et al (2013) Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 310:1473–1481

  32. 32.

    Pelzer U, Schwaner I, Stieler J et al (2011) Best supportive care (BSC) versus oxaliplatin, folinic acid and 5‑fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer 47:1676–1681

  33. 33.

    Pishvaian MJ, Bender RJ, Halverson D et al (2018) Molecular profiling of patients with pancreatic cancer: initial results from the know your tumor initiative. Clin Cancer Res 24:5018–5027

  34. 34.

    Rahib L, Smith BD, Aizenberg R et al (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74:2913–2921

  35. 35.

    Raufi AG, Manji GA, Chabot JA et al (2019) Neoadjuvant treatment for pancreatic cancer. Semin Oncol 46:19–27

  36. 36.

    Schmitt A, Feldmann G, Zander T et al (2018) Targeting defects in the cellular DNA damage response for the treatment of pancreatic ductal adenocarcinoma. Oncol Res Treat 41:619–625

  37. 37.

    Seufferlein T, Hammel P, Delpero JR et al (2019) Optimizing the management of locally advanced pancreatic cancer with a focus on induction chemotherapy: expert opinion based on a review of current evidence. Cancer Treat Rev 77:1–10

  38. 38.

    Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34

  39. 39.

    Singhi AD, George B, Greenbowe JR et al (2019) Real-time targeted genome profile analysis of pancreatic ductal adenocarcinomas identifies genetic alterations that might be targeted with existing drugs or used as Biomarkers. Gastroenterology 156:2242–2253e4

  40. 40.

    Tempero MA, Reni M, Riess H et al (2019) APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma. J Clin Oncol 37:4000–4000

  41. 41.

    Van Mackelenbergh MG, Stroes CI, Spijker R et al (2019) Clinical trials targeting the stroma in pancreatic cancer: a systematic review and meta-analysis. Cancers 11:588

  42. 42.

    Versteijne E, Vogel JA, Besselink MG et al (2018) Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg 105:946–958

  43. 43.

    Von Hoff DD, Ervin T, Arena FP et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691–1703

  44. 44.

    Waddell N, Pajic M, Patch AM et al (2015) Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 518:495–501

  45. 45.

    Wang-Gillam A, Li CP, Bodoky G et al (2016) Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet 387:545–557

  46. 46.

    Wattenberg MM, Asch D, Yu S et al (2019) Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation. Br J Cancer. https://doi.org/10.1038/s41416-019-0582-7

  47. 47.

    Wolfe AR, Miller ED, Abushahin LI et al (2019) Neoadjuvant FOLFIRINOX versus adjuvant gemcitabine in pancreatic cancer. J Clin Oncol 37:4123–4123

  48. 48.

    Yarchoan M, Myzak MC, Johnson BA 3rd et al (2017) Olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients with advanced pancreatic cancer. Oncotarget 8:44073–44081

  49. 49.

    Zorde Khvalevsky E, Gabai R, Rachmut IH et al (2013) Mutant KRAS is a druggable target for pancreatic cancer. Proc Natl Acad Sci U S A 110:20723–20728

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Author information

Correspondence to PD Dr. med. Georg Feldmann.

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Interessenkonflikt

G. Feldmann gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden vom Autor keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Feldmann, G. Medikamentöse Therapie des Pankreaskarzinoms. Internist 61, 226–232 (2020). https://doi.org/10.1007/s00108-020-00750-y

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Schlüsselwörter

  • Duktales Adenokarzinom des Pankreas
  • Molekular zielgerichtete Therapie
  • Immuntherapie
  • Humanes KRAS
  • Palliativversorgung

Keywords

  • Ductal adenocarcinoma, pancreatic
  • Molecular targeted therapy
  • Immunotherapy
  • KRAS protein, human
  • Palliative care