Therapieempfehlung für das metastasierte nicht-kleinzellige Lungenkarzinom

 

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Zusammenfassung

Das Lungenkarzinom ist weiterhin die häufigste zum Tode führende Krebserkrankung in Deutschland und durch eine frühe Metastasierung charakterisiert. Die systemische Therapie insbesondere des metastasierten, nicht-kleinzelligen Lungenkarzinoms (NSCLC) hat sich in den letzten Jahren durch die Identifikation von behandelbaren molekularen Alterationen und durch Einführung neuer Medikamente wie Tyrosinkinaseinhibitoren, Angiogeneseinhibitoren und Immunmodulatoren deutlich erweitert. Diese raschen Veränderungen der therapeutischen Möglichkeiten stellen auch eine Herausforderung für den behandelnden Arzt dar und erfordern neue diagnostische Vorgehensweisen sowie die Bildung molekular, histologisch oder klinisch definierter Patientensubgruppen. Zudem werden supportive Möglichkeiten immer bedeutsamer. Mit der Therapieempfehlung soll ein kurzer Überblick über aktuelle Therapieentwicklungen beim metastasierten NSCLC gegeben werden.

Abstract

Lung cancer accounts for the leading cause of cancer deaths in Germany and is characterized by early metastasis formation. The majority of patients with non-small cell lung cancer (NSCLC) will receive systemic therapy for treatment of their disease. Importantly together with the identification of targetable oncogenic alterations, systemic treatment of NSCLC has dramatically changed in recent years with the implementation of various new agents such as tyrosine kinase inhibitors, anti angiogenic agents, and immune modulating drugs. However, these new therapeutic options also challenge the treating physician since molecular, histologic, and clinical factors need to be considered for the clinical decision-making. Moreover, supportive therapy including bronchoscopic therapy has evolved. The following therapy recommendations will summarize the up-to date treatment strategies for metastatic NSCLC.

• Literatur

• 1 Malvezzi M, Bertuccio P, Rosso T et al. European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women?. Ann Oncol 2015; 26: 779-786
  CrossrefPubMedGoogle Scholar
• 2 Goeckenjan G, Sitter H, Thomas M et al. Prevention, diagnosis, therapy, and follow-up of lung cancer: interdisciplinary guideline of the German Respiratory Society and the German Cancer Society. Pneumologie 2010; 65: 39-59
  Article in Thieme ConnectPubMedGoogle Scholar
• 3 Reck M, Popat S, Reinmuth N et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25 (Suppl. 03) iii27-39
  CrossrefPubMedGoogle Scholar
• 4 Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest 2009; 136: 260-271
  CrossrefPubMedGoogle Scholar
• 5 Goldstraw P, Chansky K, Crowley J et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2016; 11: 39-51
  CrossrefPubMedGoogle Scholar
• 6 Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-247
  CrossrefPubMedGoogle Scholar
• 7 Travis WD, Brambilla E, Burke AP et al. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. J Thorac Oncol 2015; 10: 1240-1242
  CrossrefPubMedGoogle Scholar
• 8 Travis WD, Brambilla E, Noguchi M et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary. Proceedings of the American Thoracic Society 2011; 8: 381-385
  CrossrefPubMedGoogle Scholar
• 9 Leighl NB, Rekhtman N, Biermann WA et al. Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the study of lung cancer/association for molecular pathology guideline. J Clin Oncol 2014; 32: 3673-3679
  CrossrefPubMedGoogle Scholar
• 10 Kerr KM, Bubendorf L, Edelman MJ et al. Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer. Ann Oncol 2014; 25: 1681-1690
  CrossrefPubMedGoogle Scholar
• 11 Soda M, Choi YL, Enomoto M et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448: 561-566
  CrossrefPubMedGoogle Scholar
• 12 Sebastian M, Niederle N, Thomas M et al. [Molecular genetic tests in advanced non-small cell lung cancer: practical relevance]. Dtsch Med Wochenschr 2014; 139: 2096-2100
  Article in Thieme ConnectPubMedGoogle Scholar
• 13 Ardizzoni A, Boni L, Tiseo M et al. Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis. Journal of the National Cancer Institute 2007; 99: 847-857
  CrossrefPubMedGoogle Scholar
• 14 Schiller JH, Harrington D, Belani CP et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. The New England journal of medicine 2002; 346: 92-98
  CrossrefPubMedGoogle Scholar
• 15 Li M, Zhang Q, Fu P et al. Pemetrexed plus platinum as the first-line treatment option for advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials. PLoS One 2012; 7: e37229
  CrossrefPubMedGoogle Scholar
• 16 Scagliotti G, Hanna N, Fossella F et al. The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies. The oncologist 2009; 14: 253-263
  CrossrefPubMedGoogle Scholar
• 17 Socinski MA, Bondarenko I, Karaseva NA et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol 2012; 30: 2055-2062
  CrossrefPubMedGoogle Scholar
• 18 Thatcher N, Hirsch FR, Luft AL et al. 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. The lancet oncology 2015; 16: 763-774
  CrossrefPubMedGoogle Scholar
• 19 Soria JC, Mauguen A, Reck M et al. Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer. Ann Oncol 2013; 24: 20-30
  CrossrefPubMedGoogle Scholar
• 20 Zhou C, Wu YL, Chen G et al. BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol 2015; 33: 2197-2204
  CrossrefPubMedGoogle Scholar
• 21 Park JO, Kim SW, Ahn JS et al. 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 2007; 25: 5233-5239
  CrossrefPubMedGoogle Scholar
• 22 Cappuzzo F, Ciuleanu T, Stelmakh L et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. The lancet oncology 2010; 11: 521-529
  CrossrefPubMedGoogle Scholar
• 23 Ciuleanu T, Brodowicz T, Zielinski C et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 2009; 374: 1432-1440
  CrossrefPubMedGoogle Scholar
• 24 Barlesi F, Scherpereel A, Rittmeyer A et al. 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 2013; 31: 3004-3011
  CrossrefPubMedGoogle Scholar
• 25 Zhang X, Zang J, Xu J et al. Maintenance therapy with continuous or switch strategy in advanced non-small cell lung cancer: a systematic review and meta-analysis. Chest 2011; 140: 117-126
  CrossrefPubMedGoogle Scholar
• 26 Paz-Ares L, de Marinis F, Dediu M et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. The lancet oncology 2012; 13: 247-255
  CrossrefPubMedGoogle Scholar
• 27 Barlesi F, Scherpereel A, Gorbunova V et al. Maintenance bevacizumab-pemetrexed after first-line cisplatin-pemetrexed-bevacizumab for advanced nonsquamous nonsmall-cell lung cancer: updated survival analysis of the AVAPERL (MO22089) randomized phase III trial. Ann Oncol 2014; 25: 1044-1052
  CrossrefPubMedGoogle Scholar
• 28 Reinmuth N, Payer N, Muley T et al. Treatment and outcome of patients with metastatic NSCLC: a retrospective institution analysis of 493 patients. Respir Res 2013; 14: 139
  CrossrefPubMedGoogle Scholar
• 29 Reck M, Kaiser R, Mellemgaard A et al. 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. The lancet oncology 2014; 15: 143-155
  CrossrefPubMedGoogle Scholar
• 30 Garon EB, Ciuleanu TE, Arrieta O et al. 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 2014; 384: 665-673
  CrossrefPubMedGoogle Scholar
• 31 Soria JC, Felip E, Cobo M et al. 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. The lancet oncology 2015; 16: 897-907
  CrossrefPubMedGoogle Scholar
• 32 Brahmer J, Reckamp KL, Baas P et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. The New England journal of medicine 2015; 373: 123-135
  CrossrefPubMedGoogle Scholar
• 33 Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. The New England journal of medicine 2015; 373: 1627-1639
  CrossrefPubMedGoogle Scholar
• 34 Lee CK, Brown C, Gralla RJ et al. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. Journal of the National Cancer Institute 2013; 105: 595-605
  CrossrefPubMedGoogle Scholar
• 35 Yang JC, Wu YL, Schuler M et al. 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. The lancet oncology 2015; 16: 141-151
  CrossrefPubMedGoogle Scholar
• 36 Seto T, Kato T, Nishio M et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol 2014; 15: 1236-1244
  CrossrefPubMedGoogle Scholar
• 37 Shaw AT, Kim DW, Nakagawa K et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. The New England journal of medicine 2013; 368: 2385-2394
  CrossrefPubMedGoogle Scholar
• 38 Solomon BJ, Mok T, Kim DW et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. The New England journal of medicine 2014; 371: 2167-2177
  CrossrefPubMedGoogle Scholar
• 39 Shaw AT, Kim DW, Mehra R et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. The New England journal of medicine 2014; 370: 1189-1197
  CrossrefPubMedGoogle Scholar
• 40 Lilenbaum R, Villaflor VM, Langer C et al. Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2: prognostic factors and treatment selection based on two large randomized clinical trials. J Thorac Oncol 2009; 4: 869-874
  CrossrefPubMedGoogle Scholar
• 41 Zukin M, Barrios CH, Pereira JR et al. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol 2013; 31: 2849-2853
  CrossrefPubMedGoogle Scholar
• 42 Quoix E, Zalcman G, Oster JP et al. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet 2011; 378: 1079-1088
  CrossrefPubMedGoogle Scholar
• 43 Sperduto PW, Kased N, Roberge D et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 2011; 30: 419-425
  PubMedGoogle Scholar
• 44 Tsao MN, Lloyd N, Wong RK et al. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev 2012; 4: CD003869
  PubMedGoogle Scholar
• 45 Temel JS, Greer JA, Muzikansky A et al. Early palliative care for patients with metastatic non-small-cell lung cancer. The New England journal of medicine 2010; 363: 733-742
  CrossrefPubMedGoogle Scholar
• 46 Bolliger CT, Mathur PN, Beamis JF et al. ERS/ATS statement on interventional pulmonology. European Respiratory Society/American Thoracic Society. Eur Respir J 2002; 19: 356-373
  CrossrefPubMedGoogle Scholar
• 47 Guibert N, Mazieres J, Marquette CH et al. Integration of interventional bronchoscopy in the management of lung cancer. Eur Respir Rev 2015; 24: 378-391
  CrossrefPubMedGoogle Scholar
• 48 Davies HE, Mishra EK, Kahan BC et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA 2012; 307: 2383-2389
  CrossrefPubMedGoogle Scholar