Pneumologie 2018; 72(02): 138-154
DOI: 10.1055/s-0043-118904
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Aktualisierte Therapieempfehlung metastasiertes nicht kleinzelliges Lungenkarzinom

Updated Recommendation for Treatment of Metastatic Non-Small Cell Lung Cancer
N. Reinmuth
1   Asklepios Fachkliniken München-Gauting, Thorakale Onkologie, Gauting
,
A. Gröschel
2   Clemenshospital Münster, Klinik für Pneumologie und Beatmungsmedizin, Münster
,
C. Schumann
3   Klinikverbund Kempten-Oberallgäu, Klinik für Pneumologie, Thoraxonkologie, Schlaf- und Beatmungsmedizin, Kempten
,
M. Sebastian
4   Universitätsklinik Frankfurt, Klinik für Innere Medizin, Hämatologie und Onkologie, Frankfurt
,
R. Wiewrodt
5   Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A, Münster
,
M. Reck
6   LungenClinic Grosshansdorf, Onkologischer Schwerpunkt, Airway Research Center North (ARCN), Deutsches Zentrum für Lungenforschung (DZL), Großhansdorf
› Author Affiliations
Further Information

Publication History

eingereicht 07 July 2017

akzeptiert nach Revision 28 August 2017

Publication Date:
21 December 2017 (online)

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 insbesondere durch die Identifikation von behandelbaren molekularen Alterationen und durch Einführung neuer Medikamente wie Tyrosinkinaseinhibitoren 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 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 decisionmaking. 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 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
  • 2 Novello S, Barlesi F, Califano R. et al. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27: v1-v27
  • 3 Bruce N, Dherani M, Liu R. et al. Does household use of biomass fuel cause lung cancer? A systematic review and evaluation of the evidence for the GBD 2010 study. Thorax 2015; 70: 433-441
  • 4 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
  • 5 Robert Koch Institut. Bericht zum Krebsgeschehen in Deutschland 2016. 2016
  • 6 Hashim D, Boffetta P, La Vecchia C. et al. The global decrease in cancer mortality: trends and disparities. Ann Oncol 2016; 27: 926-933
  • 7 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
  • 8 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
  • 9 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
  • 10 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
  • 11 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
  • 12 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
  • 13 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
  • 14 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
  • 15 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
  • 16 Shaw AT, Kim DW, Mehra R. et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 2014; 370: 1189-1197
  • 17 Warth A, Weichert W, Reck M. et al. [ROS1-Translocations in Non-Small Cell Lung Cancer]. Pneumologie 2015; 69: 477-482
  • 18 Scheel AH, Dietel M, Heukamp LC. et al. [Predictive PD-L1 immunohistochemistry for non-small cell lung cancer : Current state of the art and experiences of the first German harmonization study]. Pathologe 2016; 37: 557-567
  • 19 Hirsch FR, McElhinny A, Stanforth D. et al. PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the "Blueprint PD-L1 IHC Assay Comparison Project". J Thorac Oncol 2016; 12: 208-222
  • 20 Reck M, Rodriguez-Abreu D, Robinson AG. et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. The New Engl J Med 2016; 375: 1823-1833
  • 21 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. J Nat Cancer Inst 2007; 99: 847-857
  • 22 Schiller JH, Harrington D, Belani CP. et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346: 92-98
  • 23 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
  • 24 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
  • 25 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
  • 26 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
  • 27 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
  • 28 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 Oncol 2015; 16: 763-774
  • 29 Langer CJ, Gadgeel SM, Borghaei H. et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. The Lancet Oncol 2016; 17: 1497-1508
  • 30 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
  • 31 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. Lancet Oncol 2010; 11: 521-529
  • 32 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
  • 33 Cicenas S, Geater SL, Petrov P. et al. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer 2016; 102: 30-37
  • 34 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
  • 35 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
  • 36 Borghaei H, Paz-Ares L, Horn L. et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 2015; 373: 1627-1639
  • 37 Brahmer J, Reckamp KL, Baas P. et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med 2015; 373: 123-135
  • 38 Herbst RS, Baas P, Kim DW. et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2015; 387: 1540-1550
  • 39 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. Lancet Oncol 2015; 16: 141-151
  • 40 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
  • 41 Goss G, Tsai CM, Shepherd FA. et al. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol 2016; 17: 1643-1652
  • 42 Mok TS, Wu YL, Ahn MJ. et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med 2017; 376: 629-640
  • 43 Shaw AT, Kim DW, Nakagawa K. et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013; 368: 2385-2394
  • 44 Solomon BJ, Mok T, Kim DW. et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014; 371: 2167-2177
  • 45 Nokihara H, Hida T, Kondo M. et al. Alectinib (ALC) versus crizotinib (CRZ) in ALK-inhibitor naive ALK-positive non-small cell lung cancer (ALK+ NSCLC): Primary results from the J-ALEX study. J Clin Oncol 2016; 34: abstr 9008
  • 46 Peters S, Camidge DR, Shaw AT. et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2017; 377: 829-838
  • 47 Shaw AT, Solomon BJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med 2015; 372: 683-684
  • 48 Planchard D, Besse B, Groen HJM. et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol 2016; 17: 984-993
  • 49 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
  • 50 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
  • 51 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
  • 52 Gaspar LE, Scott C, Murray K. et al. Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases. Int J Radiat Oncol Biol Phys 2000; 47: 1001-1006
  • 53 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
  • 54 Henry DH, Costa L, Goldwasser F. et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 2011; 29: 1125-1132
  • 55 Scagliotti GV, Hirsh V, Siena S. et al. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol 2012; 7: 1823-1829
  • 56 Temel JS, Greer JA, Muzikansky A. et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010; 363: 733-742
  • 57 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
  • 58 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
  • 59 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
  • 60 Asamura H, Chansky K, Crowley J. et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the N Descriptors in the Forthcoming 8th Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2015; 10: 1675-1684