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Aktueller Stand der Therapie beim Lungenkarzinom (S.16–22)
Frank Griesinger

  1. Lary A. Robinson, Henry Wagner, Jr. and John C. Ruckdeschel Treatment of Stage IIIA Non-small Cell Lung Cancer Chest 2003; 123;202–220. DOI: 10.1378/chest.123.1_suppl.202S
  2. www.onkopedia.com/de/onkopedia/guidelines/lungenkarzinom-nicht-kleinzellig-nsclc/@@view/html/index.html
  3. Wakelee et al. ASCO 2016
  4. NSCLC Metaanalysis Cooperative Group, Lancet 2014 (383): 1561–71
  5. Song WA et al, JTO 2010 (5): 510–6
  6. Miklos Pless, Roger Stupp, Hans-Beat Ris, Rolf A Stahel, Walter Weder et al. Induction chemoradiation in stage IIIA/N2 non-small-celllung cancer: a phase 3 randomised trial. Lancet 2015; 386: 1049–56
  7. Kelly K, Altorki NK, Eberhardt WE, O'Brien ME, Spigel D et al. Adjuvant Erlotinib Versus Placebo in Patients With Stage IB-IIIA Non-Small-Cell Lung Cancer (RADIANT): A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2015 Dec 1; 33(34): 4007–14
  8. Wu et al. Gefitinib (G) versus vinorelbine/cisplatin (VP) as adjuvant treatment in stage II-IIIA (N1-N2) non –small cell lung cancer (NSCLC) with EGFR activating mutation (ADJUVANT): a randomized, Phase III Trial (CTONG 1104). PASCO 2017; #8500
  9. Pöttgen C et al. Oncotarget. 2017 Mar 22. doi: 10.18632/oncotarget.16471 
  10. S.J. Antonia, A. Villegas, D. Daniel, D. Vicente, S. Murakami, R. Hui et al. Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. DOI: 10.1056/NEJMoa1709937
  11. www.astrazeneca-us.com/media/press-releases/2017/imfinzi-durvalumab-significantly-reduces-the-risk-of-disease-worsening-or-death-in-the-phase-iii-pacific-trial-for-stage-iii-unresectable-lung-cancer-05152017.html
  12. Eberhardt WE, Mitchell A, Crowley J, Kondo H, Kim YT et al. The IASLC Lung Cancer Staging Project: Proposals for the Revision of the M Descriptors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer.J Thorac Oncol. 2015 Nov; 10(11): 1515–22. doi: 10.1097/JTO.0000000000000673. Review
  13. Fabrice Barlesi, Julien Mazieres, Jean-Philippe Merlio, Didier Debieuvre, Jean Mosser et al. Routine molecular profi ling 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: 1415–26
  14. Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D et al. MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression.  J Clin Oncol. 2016 Mar 1; 34(7): 721–30
  15. Mok T et al. Dacomitinib versus Gefitinib for the first line treatment of advanced NSCLC (ARCHER 1050): a randomized , open label Phase 3 trial. PASCO 2017 
  16. Ramalingam S et al. Osimertinib vs. standard of are EGFR –TKI as first line treatment in patients withEGFRm advanced NSCLC: FLAURA: ESMO 2017
  17. T.S. Mok, Y.-L. Wu, M.-J. Ahn, M.C. Garassino, H.R. Kim et al. Papadimitrakopoulou, for the AURA3 Investigators. Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer NEJM 2016. DOI: 10.1056/NEJMoa1612674
  18. Duruisseaux M, Besse B, Cadranel J, Pérol M, Mennecier B et al. Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study. Oncotarget. 2017 Mar 28; 8(13): 21903–17. doi: 10.18632/oncotarget.15746
  19. Solange Peters, M.D., Ph.D., D. Ross Camidge, M.D., Ph.D., Alice T. Shaw, M.D., Ph.D., Shirish Gadgeel, M.D., Jin S. Ahn et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer. NEJM 2017 DOI: 10.1056/NEJMoa1704795 
  20. Justin F. Gainor , Leila Dardaei , Satoshi Yoda , Luc Friboulet , Ignaty Leshchiner et al. Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK -Rearranged Lung Cancer. Cancer Discovery 2016. DOI: 10.1158/2159-8290.CD-16-0596
  21. Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20; 371(21): 1963–71. doi: 10.1056/NEJMoa1406766. Epub 2014 Sep 27
  22. Mazières J, Zalcman G, Crinò L, Biondani P, Barlesi F et al. Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort. J Clin Oncol. 2015 Mar 20; 33(9):992–9. doi: 10.1200/JCO.2014.58.3302. Epub 2015 Feb 9
  23. Planchard D, Besse B, Groen HJ, Souquet PJ, Quoix E 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 Jul; 17(7): 984–93. doi: 10.1016/S1470-2045(16)30146-2. Epub 2016 Jun 6
  24. Awad M et al.  Impact of MET inhibitors on survival among patients (pts) with MET exon 14 mutant (METdel14) non-small cell lung cancer (NSCLC). PASCO 2017 # 8511
  25. Gautschi O, Milia J, Filleron T, Wolf J, Carbone DP et al. Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry. J Clin Oncol. 2017 May 1; 35(13): 1403–1410. doi: 10.1200/JCO.2016.70.9352. Epub 2017 Mar 13
  26. Julie Brahmer, M.D., Karen L. Reckamp, M.D., Paul Baas, M.D., Lucio Crinò, M.D., Wilfried E.E. Eberhardt, M.D. et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer N Engl J Med 2015; 373: 123–35. DOI: 10.1056/NEJMoa1504627
  27. H. Borghaei, L. Paz‑Ares, L. Horn, D.R. Spigel, M. Steins et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer N Engl J Med 2015; 373:1627–39. DOI:10.1056/NEJMoa1507643
  28. Roy S Herbst, Paul Baas, Dong-Wan Kim, Enriqueta Felip, José L Pérez-Gracia et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial Lancet 2016. doi.org/10.1016/S0140-6736(15)01281-7
  29. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F et al.  Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017 Jan 21; 389(10066): 255–65. doi: 10.1016/S0140-6736(16)32517-X. Epub 2016 Dec 13
  30. Martin Reck, Delvys Rodriguez-Abreu, Andrew G. Robinson, Rina Hui, Tibor Csőszi et al. Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer. N Engl J Med 2016; 375: 1823–33. DOI: 10.1056/NEJMoa1606774
  31. Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M et al. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Jun 22; 376(25): 2415–26. doi: 10.1056/NEJMoa1613493

  

Immuntherapie beim nicht-kleinzelligen Lungenkarzinom (S.23–26)
Niels Reinmuth, ThomasDuell

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144: 646–674
  2. Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy-inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res 2012;18: 6580–87
  3. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366: 2455–65
  4. 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: 1627–39
  5. 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: 1540–50
  6. Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 2016;389: 255–65
  7. Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2016;375: 1823–33
  8. Brahmer JR, Rodriguez-Abreu D, Robinson AG, et al. Progression After the Next Line of Therapy (PFS2) and Updated OS Among Patients with Advanced NSCLC and PD-L1 TPS >=50 % enrolled in KEYNOTE-024. J Clin Oncol 2017;35: abstr 9000
  9. Carbone DP, Reck M, Paz-Ares L, et al. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med 2017;376: 2415–26
  10. Eigentler TK, Hassel JC, Berking C, et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treatment Reviews 2016;45: 7–18
  11. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med 2017
  12. Hellmann MD, Rizvi NA, Goldman JW, et al. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Lancet Oncol 2016;18: 31–41
  13. Antonia S, Goldberg SB, Balmanoukian A, et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol 2016;17: 299–308
  14. 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. Lancet Oncol 2017;17: 1497–508
  15. Liu SV, Camidge DR, Gettinger SN, et al. First-line carboplatin and pemetrexed (CP) with or without pembrolizumab (pembro) for advanced nonsquamous NSCLC: Updated results of KEYNOTE-021 cohort G. J Clin Oncol 2017;35: abstr 9094
  16. Waterhouse DM, Goldman JW, George B, et al. Nivolumab (nivo) + nab-paclitaxel (nab-P) + carboplatin (C) in patients (pts) with non-small cell lung cancer (NSCLC): Interim results from a multicenter phase I study. J Clin Oncol 2017;35: abstr 9095

  

Das DETECT-Studienkonzept – Individualisierte Therapie des Metastasierten Mammakarzinoms auf der Grundlage von zirkulierenden Tumorzellen (S.32–36)
Polasik Arkadius1, Schochter Fabienne1, Tzschaschel Marie1, de Gregorio Amelie1, Romashova Tatiana1, Friedl Thomas WP1, Rack Brigitte2, Fasching Peter A3, Taran Florin-Andrei4, Heinrich Georg, Hartkopf Andreas4, Schneeweiss Andreas5, Müller Volkmar6, Huober Jens1, Janni Wolfgang1, Fehm Tanja7

  1. Aktuelle Empfehlungen zur Diagnostik und Therapie primärer und metastasierter Mammakarzinome der Kommission MAMMA in der AGO e.V. wwwago-online.de 2017.
  2. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A et al(2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl JMed366(10):883–892
  3. Paget S (1889) Distribution of secondary growths in cancerof the breast. Lancet1:571
  4. Braun S et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med353(8):793–802
  5. Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Jückstock J, Borgen E et al (2011) Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse – a European pooled analysis. Clin Cancer Res17(9):2967–2976
  6. Fehm T, Muller V, Aktas B, Janni W, Schneeweiss A, Stickeler E, Lattrich C et al (2010) HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat124(2):403–412
  7. Bidard F-C, Peeters DJ, Fehm T et al (2015) Clinical validity of circulationg tumor cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. LancetOncol15:406–415
  8. 11. Bidard FC, Peeters DJ, Fehm T, Nolé F, GisbertCriado R, Mavroudis D, Grisanti S et al (2014) Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol 15(4):406–414
  9. Yang YF, Liao YY, Yang M, Peng NF, Xie SR, Xie YF (2014) Discordances in ER, PR and HER2 receptors between primaryand recurrent/metastaticlesions and their impact on survival in breast
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  11. Somlo G, Lau SK, Frankel P, Hsieh HB, Liu X, Yang L, Krivacic R, Bruce RH (2011) Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/ inflammatory, and stage IV breast cancer, using a novel detection technology. Breast Cancer Res Treat128(1):155–163
  12. Munzone E, Nolé F, Goldhirsch A, Botteri E et al (2010) ChangesofHER2 status in circulating tumor cells compared with the primary tumor during treatment for advanced breast cancer. Clin Breast Cancer10(5):392–397
  13. Jäger BA, Finkenzeller C, Bock C, Majunke L, Jückstock JK et al (2015) Estrogen receptor and HER2 status on disseminated tumor cells and primary tumor in patientswith early breast cancer. TranslOncol8(6):509–516
  14. Santinelli A, Pisa E, Stramazzotti D, Fabris G (2008) HER-2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy. Int J Cancer122:999–1004
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  20. Eichhorn PJA, Gili M, Scaltriti M et al (2008) Phosphatidyinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res68:9221–30
  21. Dupont Jensen J, Laenkholm A-V, Knoop A et al (2011) PIK3CA mutations might be discordant between primary and corresponding metastatic disease in breast cancer. Clin Cancer Res 17:667–77

 

PHARMAFORUM:
Neuzulassung: Erster PD-L1-Inhibitor beim Lungen- und Urothelkarzinom
Tecentriq: Überzeugend wirksam und verträglich (S. 52–53, Roche Pharma AG)

  1. Fachinformation Tecentriq®, Stand September 2017 
  2. Balar AV et al., Lancet 2017; 389(10064): 67–76 
  3. Loriot Y et al., ESMO 2016; Abstract 783P 
  4. Powles T et al., EACR-AACR-SIC 2017 (Special conference). Juni 2017, Abstract 606 
  5. Rittmeyer A et al., Lancet 2017, 389(10066): 255–65 
  6. Herbst RS et al,. Nature 2014; 515: 563–67 
  7. Chen DS et al., Clin Cancer Res 2012; 18: 6580–87 
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  9. Pardoll DM., Nat Rev Cancer 2012; 12: 252–64 
  10. Sznol M, Chen L., Clin Cancer Res 2013; 19: 1021–34 
  11. Murphy K et al. Janeway’s Immunobiology. 8th ed. New York: Garland Science; 2012: S. 5–1 
  12. Butte MJ et al., Immunity 2007; 27: 111–22 
  13. Yang J et al., J Immunol 2011; 187: 1113–19 
  14. Schmid P et al., J Clin Oncol 2016; 34 (suppl): Abstract 11506 
  15. Latchman Y et al., Nature Immunol 2001; 2: 261–268 
  16. Akbari O et al., Mucosal Immunol 2010; 3: 81–91 
  17. De Santis M et al., J Clin Oncol 2012, 30: 191–99 
  18. S3-Leitlinie: Früherkennung, Diagnose, Therapie und Nachsorge des Harnblasenkarzinoms. Kurzversion 1.1 – November 2016. Register: 032/038OL

PHARMAFORUM:
Cabozantinib beim metastasierten Nierenzellkarzinom
Multi-Target-Kinase-Inhibitor: Überzeugende Daten in der Zweitlinientherapie
(S. 56, Ipsen Pharma GmbH)

  1. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015; 373(19): 1814–23 
  2. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul; 17(7): 917–27
  3. Choueiri TK et al. ESMO 2017, Poster LBA38