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Medikamentöse Therapie des metastasierten oder rezidivierten mutationsnegativen NSCLC

Medicinal treatment of metastatic or recurrent NSCLC without driver mutations

  • Leitthema
  • Published:
Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Die Behandlung des metastasierten nichtkleinzelligen Lungenkarzinoms (NSCLC) ohne behandelbare Treibermutation hat sich in den vergangenen Jahren insbesondere durch die Einführung der Immuncheckpointinhibitoren (ICI) rasch verändert.

Ziel

Ein kurzer historischer Abriss sowie der aktuelle Stand der Behandlung des NSCLC Stadium IV sollen knapp zusammengefasst werden.

Material und Methoden

Eine selektive Literaturrecherche der Datenbank Pubmed wurde durchgeführt. Suchbegriffe: NSCLC stage IV, checkpointinhibitors, chemotherapy.

Schlussfolgerung

Immuncheckpointinhibitoren wurden zunächst in der Zweitlinientherapie eingeführt, weil sie sich in mehreren großen Phase-III-Studien einer Standard-Docetaxel-Therapie als deutlich überlegen erwiesen hatten. Mittlerweile wird Pembrolizumab als Standard-Erstlinientherapie bei hoher Programmed-death-ligand-1(PD-L1)-Expression (Tumor Proportion Score [TPS] > 50 %) eingesetzt. In mehreren Phase-III-Studien hat sich eine Kombination mit ICI und Chemotherapie in der Erstlinientherapie einer Standardchemotherapie als überlegen erwiesen. Zulassungen für die Kombinationserstlinientherapie liegen für das nichtsquamöse NSCLC (nsNSCLC) bereits vor und weitere Zulassungen sind zu erwarten. Erst seit Einführung der ICI lässt sich bei einem Teil der Patienten mit metastasiertem NSCLC ein Langzeitüberleben von 3 Jahren und mehr erzielen.

Abstract

Background

The introduction of immune checkpoint inhibitors (ICI) has led to rapid changes in the treatment of metastatic non-small cell lung cancer (NSCLC) without treatable driver mutations over the last few years.

Objective

A brief historical outline of treatment before and a summary of changes after the arrival of ICI is given.

Material and methods

A selective Pubmed search was performed employing the keywords NSCLC stage IV, checkpoint inhibitors and chemotherapy.

Conclusion

The ICIs were initially introduced as second line treatment of metastatic NSCLC as several large phase III trials were able to show a clinically significant improvement compared to the standard docetaxel treatment. Meanwhile, pembrolizumab is the standard first-line treatment of NSCLC with high PD-L1 expression (TPS > 50%). Recently, several phase III trials could show superior efficacy of the combination of an ICI with standard platinum-based doublet chemotherapy compared to chemotherapy alone. Some of the investigated combinations have already been approved for nonsquamous NSCLC and further approvals can be expected. Since the introduction of ICI long-term survival of 3 or more years has been achieved in some patients with metastatic NSCLC.

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Abb. 1

Notes

  1. In Studien mit Atezolizumab verwendetes TC/IC-Scoring-System: TC = „tumour cells“, Tumorzellen, die positiv sind für PD-L1, TC 0 = < 1 %, TC 1 = 1–5 %, TC 2 = 5–49 %, TC 3 = >50 %; IC = „immune cells“, Fläche des Immunzellinfiltrats, welches positiv ist für PD-L1, IC 0 = < 1 %, IC 1 = 1–5 %, IC 2 = 5–9 %, IC 3 = > 10 %.

Literatur

  1. Non-small Cell Lung Cancer Collaborative Group (1995) Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ 311(7010):899–909

    Article  Google Scholar 

  2. Abratt RP, Hart GJ (2006) 10-year update on chemotherapy for non-small cell lung cancer. Ann Oncol 17(Suppl 5: p):v33–36

    Article  Google Scholar 

  3. Shepherd FA et al (2000) Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 18(10):2095–2103

    Article  CAS  Google Scholar 

  4. Hanna N et al (2004) Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 22(9):1589–1597

    Article  CAS  Google Scholar 

  5. Shepherd FA et al (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353(2):123–132

    Article  CAS  Google Scholar 

  6. Scagliotti GV et al (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26(21):3543–3551

    Article  CAS  Google Scholar 

  7. Kawaguchi T et al (2014) Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol 32(18):1902–1908

    Article  CAS  Google Scholar 

  8. Soria JC et al (2015) Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol 16(8):897–907

    Article  CAS  Google Scholar 

  9. Rossi A et al (2014) Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data. Lancet Oncol 15(11):1254–1262

    Article  Google Scholar 

  10. Smith IE et al (2001) Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol 19(5):1336–1343

    Article  CAS  Google Scholar 

  11. Park JO et al (2007) Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol 25(33):5233–5239

    Article  CAS  Google Scholar 

  12. Pirker R (2002) Two- versus three-drug combinations in the chemotherapy of advanced non-small-cell lung cancer. Lung Cancer 38(Suppl 3: p):S53–5

    Article  Google Scholar 

  13. Sandler A et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550

    Article  CAS  Google Scholar 

  14. Thatcher N et al (2015) Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol 16(7):763–774

    Article  CAS  Google Scholar 

  15. Paz-Ares LG et al (2013) PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 31(23):2895–2902

    Article  CAS  Google Scholar 

  16. Barlesi F et al (2013) Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089). J Clin Oncol 31(24):3004–3011

    Article  CAS  Google Scholar 

  17. Garon EB et al (2014) Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 384(9944):665–673

    Article  CAS  Google Scholar 

  18. Reck M et al (2014) Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol 15(2):143–155

    Article  CAS  Google Scholar 

  19. Gridelli C et al (2008) Second-line treatment of advanced non-small cell lung cancer. J Thorac Oncol 3(4):430–440

    Article  Google Scholar 

  20. Reck M et al (2016) Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med 375(19):1823–1833

    Article  CAS  Google Scholar 

  21. Gandhi L et al (2018) Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med 378(22):2078–2092

    Article  CAS  Google Scholar 

  22. Socinski MA et al (2018) Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med 378(24):2288–2301

    Article  CAS  Google Scholar 

  23. Leonardi GC et al (2018) Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders. J Clin Oncol 36(19):1905–1912

    Article  Google Scholar 

  24. Borghaei H et al (2015) Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 373(17):1627–1639

    Article  CAS  Google Scholar 

  25. Brahmer J et al (2015) Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med 373(2):123–135

    Article  CAS  Google Scholar 

  26. Herbst RS et al (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387(10027):1540–1550

    Article  CAS  Google Scholar 

  27. Rittmeyer A et al (2017) Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 389(10066):255–265

    Article  Google Scholar 

  28. Tazdait M et al (2018) Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy: Comparison of RECIST 1.1, irRECIST and iRECIST criteria. Eur J Cancer 88:38–47

    Article  CAS  Google Scholar 

  29. Gettinger SN et al (2018) Clinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors in 26 Patients With Advanced Non-Small Cell Lung Cancer. J Thorac Oncol 13(6):831–839

    Article  Google Scholar 

  30. Hellmann MD et al (2018) Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med 378(22):2093–2104

    Article  CAS  Google Scholar 

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Correspondence to Achim Rittmeyer.

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Interessenkonflikt

A. Rittmeyer hat Honorare als Sprecher oder Berater folgender Firmen angenommen: AbbVie, Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Pfizer, Roche.

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

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Rittmeyer, A. Medikamentöse Therapie des metastasierten oder rezidivierten mutationsnegativen NSCLC. Onkologe 24, 1003–1008 (2018). https://doi.org/10.1007/s00761-018-0474-0

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