Skip to main content
SpringerLink
Log in

Die personalisierte Therapie des Lungenkarzinoms

Personalized treatment of lung cancer

  • Leitthema
  • Published:
Der Pneumologe Aims and scope

Zusammenfassung

In der Therapie des Lungenkarzinoms gab es in den letzten Jahren mit der Zulassung neuer Wirkstoffe und dem fortschreitenden Wissen über verschiedene Pathomechanismen grundlegende Veränderungen. Für Patienten mit einem nicht-kleinzelligen Lungenkarzinom (NSCLC) im Stadium IV stehen bei genetischer Treibermutation oder -fusion zielgerichtete Therapien zur Verfügung. Tumore mit einer Mutation des epidermalen Wachstumsfaktorrezeptors (EGFR) oder einer Translokation der anaplatischen Lymphomkinase (ALK) sollten eine spezifische Therapie mit einem Tyrosinkinaseinhibitor erhalten. Bei selteneren Mutationen werden Therapien im Rahmen von klinischen Studien angeboten. Bei einem NSCLC im Stadium IV ohne Treibermutation kann der immuntherapeutische Checkpoint-Inhibitor Pembrolizumab in Kombination mit einem platinhaltigen Zytostatikum (Cisplatin oder Carboplatin) und Pemetrexed bei nichtplattenepithelialer Histologie appliziert werden. Bei NSCLC im Stadium III kann Patienten mit einem positiven PD-L1-Status (Programmed Cell Death Ligand 1) nach Radiochemotherapie eine Konsolidierungstherapie mit dem Checkpoint-Inhibitor Durvalumab angeboten werden. Beim fortgeschrittenen kleinzelligen Lungenkarzinom (SCLC) stellt die Chemotherapie nach wie vor die wichtigste Therapiesäule dar. Auch beim SCLC zeigen neue Daten den Stellenwert der Immuntherapie.

Abstract

There have been fundamental changes in the treatment of lung cancer in recent years with advances in molecular biology leading to the approval of new medications. For patients with stage IV non-small cell lung cancer (NSCLC) targeted therapies are available for genetic driver mutations or fusions. Tumors with an epidermal growth factor receptor (EGFR) gene mutation or a translocation in the anaplastic lymphoma kinase (ALK) gene should receive specific treatment with a tyrosine kinase inhibitor. For less common mutations, treatment is offered within the framework of clinical trials. In stage IV NSCLC without a driver mutation, the immunotherapeutic checkpoint inhibitor pembrolizumab can be administered in combination with a platinum-containing cytostatic agent (cisplatin or carboplatin) and pemetrexed for non-squamous epithelium histology. In stage III NSCLC, patients with a positive programmed cell death ligand 1 (PD-L1) status can be offered consolidation therapy with the checkpoint inhibitor durvalumab after radiochemotherapy. In advanced small cell lung cancer (SCLC) chemotherapy is still the most important pillar of treatment. There is also growing evidence for the use of immunotherapy in SCLC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Barlesi F, Nishio M, Cobo M, Steele N, Paramonov V et al (2018) LBA54IMpower132: Efficacy of atezolizumab (atezo) + carboplatin (carbo)/cisplatin (cis) + pemetrexed (pem) as 1L treatment in key subgroups with stage IV non-squamous non-small cell lung cancer (NSCLC). Ann Oncol 29(suppl_8):mdy424.066

    Article  Google Scholar 

  2. Carbone D (2018) Abstract 8507. ASCO Annual Meeting, Chicago, June 1–5 2018

    Google Scholar 

  3. Chung H (2018) Abstract 8506. ASCO Annual Meeting, Chicago, June 1–5 2018

    Google Scholar 

  4. Davis AA, Chae YK, Agte S, Pan A, Mohindra NA et al (2017) Association of tumor mutational burden with smoking and mutation status in non-small cell lung cancer (NSCLC). J Clin Oncol 35(7_suppl):24

    Google Scholar 

  5. Faivre-Finn C, Spigel DR, Senan S, Langer CJ, Raben D et al (2018) 1363OEfficacy and safety evaluation based on time from completion of radiotherapy to randomization with durvalumab or placebo in pts from PACIFIC. Ann Oncol 29(suppl_8):mdy291

    Article  Google Scholar 

  6. Gainor JF, Dardaei L, Yoda S, Friboulet L, Leshchiner I et al (2016) Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov 6(10):1118–1133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E et al (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378:2078–2092. https://doi.org/10.1056/NEJMoa1801005

    Article  CAS  PubMed  Google Scholar 

  8. Hanna N, Johnson D, Temin S, Baker S, Brahmer J et al (2017) Systemic therapy for stage IV non-small-cell lung cancer: American Society of clinical oncology clinical practice guideline update. J Clin Oncol 35(30):3484–3515

    Article  CAS  PubMed  Google Scholar 

  9. Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M et al (2018) First-line Atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. https://doi.org/10.1056/NEJMoa1809064

    Article  PubMed  Google Scholar 

  10. Johung KL, Yeh N, Desai NB, Williams TM, Lautenschlaeger T et al (2016) Extended survival and prognostic factors for patients with ALK-rearranged non-small-cell lung cancer and brain metastasis. J Clin Oncol 34(2):123–129

    Article  CAS  PubMed  Google Scholar 

  11. Li B, Huang X, Fu L (2018) Impact of smoking on efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer patients: a meta-analysis. Onco Targets Ther 11:3691–3696

    Article  PubMed  PubMed Central  Google Scholar 

  12. Middleton G, Brock K, Summers Y, Connibear J, Shah R, Billingham L (2018) Pembrolizumab in performance status 2 patients with non-small-cell lung cancer (NSCLC): results of the PePS2 trial. Ann Oncol 29(suppl_8):493–547

    Google Scholar 

  13. Mok TS, Wu Y‑L, Ahn M‑J, Garassino MC, Kim HR et al (2017) Osimertinib or platinum-Pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 376(7):629–640

    Article  CAS  PubMed  Google Scholar 

  14. Novello S, Barlesi F, Califano R, Cufer T, Ekman S et al (2016) Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 27:V1–V27

    Article  CAS  PubMed  Google Scholar 

  15. Paz-Ares L, Tan EH, O’Byrne K, Zhang L, Hirsh V et al (2017) Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-lung 7 trial. Ann Oncol 28(2):270–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, Kowalski DM (2018) Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. https://doi.org/10.1056/NEJMoa1810865

    Article  PubMed  PubMed Central  Google Scholar 

  17. Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS et al (2017) Alectinib versus Crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. https://doi.org/10.1056/NEJMoa1704795

    Article  PubMed  PubMed Central  Google Scholar 

  18. Quoix E, Audigier Valette C, Lavolé A, Molinier O, Westeel V et al (2018) LBA56Maintenance chemotherapy versus follow-up after carboplatin and weekly paclitaxel doublet chemotherapy in elderly patients with advanced non-small cell lung cancer (NSCLC): IFCT-1201 MODEL randomised phase III trial. Ann Oncol 29(suppl_8):mdy424.068

    Article  Google Scholar 

  19. Ramalingam SS, Yang JCH, Lee CK, Kurata T, Kim DW et al (2018) Osimertinib as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer. J Clin Oncol 36(9):841–849

    Article  CAS  PubMed  Google Scholar 

  20. Sequist LV, Yang JCH, Yamamoto N, O’Byrne K, Hirsh V et al (2013) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31(27):3327–3334

    Article  CAS  PubMed  Google Scholar 

  21. Soria J‑C, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B et al (2017) Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. https://doi.org/10.1056/NEJMoa1713137

    Article  PubMed  Google Scholar 

  22. Velcheti V, Kim ES, Mekhail T, Dakhil C, Stella PJ et al (2018) Prospective clinical evaluation of blood-based tumor mutational burden (bTMB) as a predictive biomarker for atezolizumab (atezo) in 1L non-small cell lung cancer (NSCLC): Interim B‑F1RST results. J Clin Oncol 36(15_suppl):12001

    Article  Google Scholar 

  23. Wang S, Tsui ST, Liu C, Song Y, Liu D (2016) EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer. J Hematol Oncol 9(1):59

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K et al (2017) Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol 18(11):1454–1466

    Article  CAS  PubMed  Google Scholar 

  25. Yang J, Ramalingam SS, Jänne PA, Cantarini M, Mitsudomi T (2016) LBA2_PR: Osimertinib (AZD9291) in pre-treated pts with T790M-positive advanced NSCLC: updated Phase 1 (P1) and pooled Phase 2 (P2) results. J Thorac Oncol 11(4):152–153

    Article  Google Scholar 

  26. Yang JCH, Wu YL, Schuler M, Sebastian M, Popat S et al (2015) Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 16(2):141–151

    Article  CAS  PubMed  Google Scholar 

  27. Yang JJ, Zhou Q, Yan HH, Zhang XC, Chen HJ et al (2017) A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. br J Cancer 116(5):568–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhang I, Zaorsky NG, Palmer JD, Mehra R, Lu B (2015) Targeting brain metastases in ALK-rearranged non-small-cell lung cancer. Lancet Oncol 16(13):e510–e521. https://doi.org/10.1016/S1470-2045(15)00013-3

    Article  CAS  PubMed  Google Scholar 

  29. Zhang J, Wu H, Li P, Zhao Y, Liu M, Tang H (2014) NF-kappaB-modulated miR-130a targets TNF-alpha in cervical cancer cells. J Transl Med 12(1):155

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zhong W‑Z, Wu Y‑L, Chen K‑N, Chen C, Gu C‑D et al (2018) LBA48_PRCTONG 1103: Erlotinib versus gemcitabine plus cisplatin as neo-adjuvant treatment for stage IIIA-N2 EGFR-mutation non-small cell lung cancer (EMERGING): A randomised study. Ann Oncol 29(suppl_8):mdy424.058

    Article  Google Scholar 

  31. Zhou C, Wu YL, Chen G, Feng J, Liu XQ et al (2015) Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol 26(9):1877–1883

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Klinik u. Poliklinik V (Pneumologie), Ludwig-Maximilians-Universität, Campus Großhadern, Marchioninistraße 15, 81377, München, Deutschland

    J. Götschke,  K. Kahnert &  A. Tufman

  2. Deutsches Zentrum für Lungenforschung (DZL) Standort Comprehensive Pneumology Center Munich (CPC‑M), München, Deutschland

    J. Götschke,  K. Kahnert &  A. Tufman

Authors
  1. J. Götschke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Kahnert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Tufman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Tufman.

Ethics declarations

Interessenkonflikt

A. Tufman weist auf folgende Beziehungen hin: Beratertätigkeit für bzw. Vortragshonorare von AstraZeneca, Novartis, Boehinger Ingelheim, Takeda, Roche und BMS. J. Götschke und K. Kahnert geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Additional information

Redaktion

J. Behr, München

E. von Mutius, München

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Götschke, J., Kahnert, K. & Tufman, A. Die personalisierte Therapie des Lungenkarzinoms. Pneumologe 16, 69–75 (2019). https://doi.org/10.1007/s10405-019-0232-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10405-019-0232-z

Schlüsselwörter

Keywords

Search

Navigation