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Fortschritte der Biomarker-stratifizierten Präzisionsmedizin

Personalisierte Therapie des Lungenkarzinoms

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InFo Onkologie Aims and scope

Der Vormarsch der personalisierten Therapie — getrieben durch die rasanten Fortschritte in der genomischen Analytik und die unerwartete Beschleunigung klinischer Entwicklungsprogramme — wandelt zunehmend das diagnostische und therapeutische Vorgehen beim fortgeschrittenen, nichtkleinzelligen Lungenkarzinom (NSCLC). Aktuell erhalten bereits circa 50 % der Patienten in der Erstlinie eine primär Biomarker-stratifizierte Behandlung durch eine zielgerichtete Therapie mit einem Tyrosinkinaseinhibitor oder eine Immuntherapie mit einem Immuncheckpointinhibitor. Der Einsatz einer biologisch-rationalen Therapie in einem präselektionierten Patientenkollektiv mit einem korrespondierenden, prädiktiven Biomarker („Schlüssel-Schloss-Prinzip“ oder Präzisionsmedizin) übersetzt sich — im Vergleich zur klassischen nicht selektiven, zytotoxischen Chemotherapie — in einen signifikanten Vorteil für die Patienten mit verbesserten Remissionsraten und verlängertem Gesamtüberleben. Aktuelle Herausforderungen beinhalten die Überwindung von Resistenzen, die Entwicklung prädiktiver Marker für die Immuntherapie und die Implementierung personalisierter Therapien in der Breite der Versorgung.

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Literatur

  1. Schiller JH et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346(2):92–8.

    Article  CAS  PubMed  Google Scholar 

  2. Reck M et al. Pembrolizumab versus Chemotherapy for PD-L1- Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016;375(19):1823–33.

    Article  CAS  PubMed  Google Scholar 

  3. The Clinical Lung Cancer Genome Project (CLCGP) and Network Genomic Medicine (NGM). A genomics-based classification of human lung tumors. Sci Transl Med. 2013;5(209):209ra153.

    Google Scholar 

  4. Kostenko A et al. Survival following implementation of next-generation sequencing in routine diagnostics of advanced lung cancer: Results of the German Network Genomic Medicine. J Clin Oncol. 2016;34(15_suppl):Abstr 9085.

    Article  Google Scholar 

  5. Barlesi F et al. Routine molecular profiling of patients with advanced non-small- cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet. 2016; 387(10026):1415–26.

    Article  CAS  PubMed  Google Scholar 

  6. Sequist LV, Lynch TJ. EGFR tyrosine kinase inhibitors in lung cancer: an evolving story. Annu Rev Med. 2008;59:429–42.

    Article  CAS  PubMed  Google Scholar 

  7. Mok TS et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–57.

    Article  CAS  PubMed  Google Scholar 

  8. Sequist LV et al. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013;31(27):3327–34.

    Article  CAS  PubMed  Google Scholar 

  9. Soria JC et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small- Cell Lung Cancer. N Engl J Med. 2018;378(2):113–25.

    Article  PubMed  Google Scholar 

  10. Ramalingam S et al. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC: FLAURA. Ann Oncol. 2017;28(suppl_5);Abstr LBA2_PR.

    Article  Google Scholar 

  11. Planchard D et al. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with untreated EGFRm advanced NSCLC: FLAURA post-progression outcomes. J Thorac Oncol. 2018;13(4 Suppl);Abstr 128O.

    Google Scholar 

  12. Fassunke J et al. Overcoming EGFRG724S-mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors. Artikel eingereicht zur Veröffentlichung.

  13. Niederst MJ et al. The allelic context of the C797S mutation acquired upon treatment with third generation EGFR inhibitors impacts sensitivity to subsequent treatment strategies. Clin Cancer Res. 2015;21(17):3924–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Thress KS et al. Acquired EGFR C797S mediates resistance to AZD9291 in advanced non-small cell lung cancer harboring EGFR T790M. Nat Med. 2015;21(6):560–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Peters S et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non- Small-Cell Lung Cancer. N Engl J Med. 2017;377(9):829–38.

    Article  CAS  PubMed  Google Scholar 

  16. Solomon BJ et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167–77.

    Article  CAS  PubMed  Google Scholar 

  17. Ou SHI et al. Alectinib in Crizotinib-Refractory ALK-Rearranged Non—Small-Cell Lung Cancer: A Phase II Global Study. J Clin Oncol. 2016; 34(7):661–8.

    Article  CAS  PubMed  Google Scholar 

  18. Soria JC et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389(10072):917–29

    Article  CAS  PubMed  Google Scholar 

  19. Gainor JF et al. Molecular Mechanisms of Resistance to First- and Second- Generation ALK Inhibitors in ALK-Rearranged Lung Cancer. Cancer Discov. 2016;6(10):1118–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Scheffler M et al. ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability. Oncotarget. 2015;6(12):10577–85.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Shaw AT et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014;371(21):1963–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Katayama R et al. Cabozantinib overcomes crizotinib resistance in ROS1 fusion positive cancer. Clin Cancer Res. 2015;21(1):166–74.

    Article  CAS  PubMed  Google Scholar 

  23. Zou HY et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc Natl Acad Sci U S A. 2015;112(11):3493–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Drilon A et al. A Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with ROS1-Rearranged Lung Cancer. Clin Cancer Res. 2016;22(10):2351–8.

    Article  CAS  PubMed  Google Scholar 

  25. Planchard D et al. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017;18(10):1307–16.

    Article  CAS  PubMed  Google Scholar 

  26. Planchard D et al. Updated survival of patients (pts) with previously treated BRAF V600E—mutant advanced non-small cell lung cancer (NSCLC) who received dabrafenib (D) or D + trametinib (T) in the phase II BRF113928 study. J Clin Oncol. 2017;35(5_suppl):Abstr 9075.

    Article  Google Scholar 

  27. Awad MM et al. Impact of MET inhibitors on survival among patients (pts) with MET exon 14 mutant (METdel14) non-small cell lung cancer (NSCLC). J Clin Oncol. 2017;35(15_suppl);Abstr 8511.

    Article  Google Scholar 

  28. Drilon AE et al. Efficacy and safety of crizotinib in patients (pts) with advanced MET exon 14-altered non-small cell lung cancer (NSCLC). J Clin Oncol. 2016;34(15_suppl);Abstr 108.

    Article  Google Scholar 

  29. Drilon A et al. Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017; 7(4):400–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Drilon A et al. Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov. 2013;3(6):630–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lin JJ et al. Clinical Activity of Alectinib in Advanced RET-Rearranged Non- Small Cell Lung Cancer. J Thorac Oncol. 2016;11(11):2027–32.

    Article  PubMed  Google Scholar 

  32. Borghaei H et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non- Small-Cell Lung Cancer. N Engl J Med. 2015;373(17):1627–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Brahmer J et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non- Small-Cell Lung Cancer. N Engl J Med. 2015;373(2):123–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Peters S et al. Impact of tumor mutation burden on the efficacy of first-line nivolumab in stage iv or recurrent non-small cell lung cancer: An exploratory analysis of CheckMate 026. Cancer Res. 2017;77(13_Suppl);Abstr CT082.

    Article  Google Scholar 

  35. Hellman MD et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med. 2018;378(22):2093–104.

    Article  Google Scholar 

  36. Rizvi N et al. Impact of tumor mutation burden on the efficacy of nivolumab or nivolumab plus ipilimumab in small cell lung cancer: An exploratory analysis of CheckMate 032. WCLC. 2017;Abstr OA 07.03a.

  37. Gandhi L et al. Pembrolizumab plus Chemotherapy in Metastatic Non—Small-Cell Lung Cancer. N Engl J Med. 2018;378(22):2078–92.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Uniklinik Köln, Köln, Deutschland

    Diana S. Y. Abdulla (Assistenzärztin der Klinik I für Innere Medizin, Studienärztin der Lung Cancer Group Cologne (LCGC) &  Jürgen Wolf (Ärztlicher Leiter des Centrums für Integrierte Onkologie (CIO) Köln, Leiter der Lung Cancer Group Cologne (LCGC)

  2. Institut für Pathologie, Uniklinik Köln, Köln, Deutschland

    Carina Heydt

  3. Klinik I für Innere Medizin, Uniklinik Köln, Kerpener Str. 62, 50937, Köln, Deutschland

    Jürgen Wolf (Ärztlicher Leiter des Centrums für Integrierte Onkologie (CIO) Köln, Leiter der Lung Cancer Group Cologne (LCGC)

Authors
  1. Diana S. Y. Abdulla
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  2. Carina Heydt
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  3. Jürgen Wolf
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Correspondence to Jürgen Wolf.

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Abdulla, D.S.Y., Heydt, C. & Wolf, J. Personalisierte Therapie des Lungenkarzinoms. Info Onkol. 21 (Suppl 1), 30–36 (2018). https://doi.org/10.1007/s15004-018-6135-z

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  • DOI: https://doi.org/10.1007/s15004-018-6135-z

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