Download PDF
TumorDiagnostik & Therapie 2016; 37(02): 79-85
DOI: 10.1055/s-0042-103154
Thieme Onkologie aktuell
© Georg Thieme Verlag KG Stuttgart · New York

What’s hot in lung cancer

F. Griesinger
1   Klinik für Hämatologie und Onkologie, Pius-Hospital, Universitätsklinik für Innere Medizin-Onkologie, Universität Oldenburg
,
L. Heukamp
2   Hämatopathologie Hamburg und NEO New Oncology AG Köln
› Author Affiliations
Further Information

Publication History

Publication Date:
18 March 2016 (online)

Also available at
    Permissions and Reprints

Einleitung

Personalisierte Therapiekonzepte, bei denen der Wirkstoff auf die genetischen Veränderungen im Tumor des Patienten abgestimmt ist, haben in den letzten Jahren zu einem Paradigmenwechsel in der Onkologie geführt. Eine umfassende molekulardiagnostische Tumorcharakterisierung vor Therapiebeginn ist daher essenziell, um die für den Patienten optimale Therapie auszuwählen. Die kontinuierlich steigende Zahl therapierbarer Genveränderungen und bekannter Resistenzmechanismen bei limitierter Verfügbarkeit von Probenmaterial stellt die molekulare Diagnostik dabei vor völlig neue Herausforderungen.

Aufgrund der bahnbrechenden Fortschritte im Bereich der Tumorgenomsequenzierung ist damit zu rechnen, dass sich die Anzahl der therapeutisch adressierbaren genetischen Veränderungen und genetisch determinierten Resistenzmechanismen noch vervielfachen wird. Dadurch stellt sich die Herausforderung, die Flut dieser verfügbaren Daten für die Routinediagnostik nutzbar zu machen, und dem Patienten damit die aktuellsten Behandlungsoptionen zu eröffnen.

 

  • Literatur

  • 1 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
    CrossrefPubMedGoogle Scholar
  • 2 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
    CrossrefPubMedGoogle Scholar
  • 3 Drilon AE, Sima CS, Somwar R et al. Phase II study of cabozantinib for patients with advanced RET-rearranged lung cancers. J Clin Oncol 2015; (suppl): abstr 8007 33
    PubMedGoogle Scholar
  • 4 Felip E, Orlov S, Park K et al. ASCEND-3: A single-arm, open-label, multicenter phase II study of ceritinib in ALKi-naive adult patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC). J Clin Oncol 2015; (suppl): abstr 8060 33
    PubMedGoogle Scholar
  • 5 Fernandez-Cuesta L, Plenker D, Osada H et al. CD74-NRG1 fusions in lung adenocarcinoma. Cancer Discov 2014; 4: 415-422
    CrossrefPubMedGoogle Scholar
  • 6 Gainor JF, Tan DS, De Pas T et al. Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib. Clin Cancer Res 2015; 21: 2745-2752
    CrossrefPubMedGoogle Scholar
  • 7 Garon EB, Rizvi NA, Hui R et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015; 372: 2018-2028
    CrossrefPubMedGoogle Scholar
  • 8 Gettinger SN, Horn L, Gandhi L et al. Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol 2015; 33: 2004-2012
    CrossrefPubMedGoogle Scholar
  • 9 Gnirke A, Melnikov A, Maguire J et al. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nat Biotechnol 2009; 27: 182-189
    CrossrefPubMedGoogle Scholar
  • 10 Hadd AG, Houghton J, Choudhary A et al. Targeted, high-depth, next-generation sequencing of cancer genes in formalin-fixed, paraffin-embedded and fine-needle aspiration tumor specimens. J Mol Diagn 2013; 15: 234-247
    CrossrefPubMedGoogle Scholar
  • 11 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; DOI: 10.1016/S0140-6736(15)01281-7. [Epub ahead of print]
    PubMedGoogle Scholar
  • 12 Heuckmann JM, Thomas RK. A new generation of cancer genome diagnostics for routine clinical use: overcoming the roadblocks to personalized cancer medicine. Ann Oncol 2015; 26: 1830-1837
    CrossrefPubMedGoogle Scholar
  • 13 Jänne PA, Yang JC, Kim DW et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med 2015; 372: 1689-1699
    CrossrefPubMedGoogle Scholar
  • 14 Kerick M, Isau M, Timmermann B et al. Targeted high throughput sequencing in clinical cancer settings: formaldehyde fixed-paraffin embedded (FFPE) tumor tissues, input amount and tumor heterogeneity. BMC Med Genomics 2011; 4: 68
    CrossrefPubMedGoogle Scholar
  • 15 Le DT, Uram JN, Wang H et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015; 372: 2509-2520
    CrossrefPubMedGoogle Scholar
  • 16 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. J Natl Cancer Inst 2013; 105: 595-605
    CrossrefPubMedGoogle Scholar
  • 17 Malchers F, Dietlein F, Schöttle J et al. Cell-autonomous and non-cell-autonomous mechanisms of transformation by amplified FGFR1 in lung cancer. Cancer Discov 2014; 4: 246-257
    CrossrefPubMedGoogle Scholar
  • 18 Mazières J, Peters S, Lepage B et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol 2013; 31: 1997-2003
    CrossrefPubMedGoogle Scholar
  • 19 Meder L, König K, Fassunke J et al. Implementing amplicon-based next generation sequencing in the diagnosis of small cell lung carcinoma metastases. Exp Mol Pathol 2015; 99: 682-686
    CrossrefPubMedGoogle Scholar
  • 20 Mok T, Spigel D, Felip E et al. ASCEND-2: A single-arm, open-label, multicenter phase II study of ceritinib in adult patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) previously treated with chemotherapy and crizotinib (CRZ). J Clin Oncol 2015; (suppl): abstr 8059 33
    PubMedGoogle Scholar
  • 21 Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-957
    CrossrefPubMedGoogle Scholar
  • 22 Ou SH, Jänne PA, Bartlett CH et al. Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC. Ann Oncol 2014; 25: 415-422
    CrossrefPubMedGoogle Scholar
  • 23 Oxnard GR, Arcila ME, Sima CS. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res 2011; 17: 1616-1622
    CrossrefPubMedGoogle Scholar
  • 24 Park K. Updated safety and efficacy results from phase I/II study of HM61713 in patients (pts) with EGFR mutation positive non-small cell lung cancer (NSCLC) who failed previous EGFR-tyrosine kinase inhibitor (TKI). J Clin Oncol 2015; (suppl): abstr 8084 33
    PubMedGoogle Scholar
  • 25 Peifer M, Fernández-Cuesta L, Sos ML et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 2012; 44: 1104-1110
    CrossrefPubMedGoogle Scholar
  • 26 Planchard D, Groen HJM, Kim TM et al. Interim results of a phase II study of the BRAF inhibitor (BRAFi) dabrafenib (D) in combination with the MEK inhibitor trametinib (T) in patients (pts) with BRAF V600E mutated (mut) metastatic non-small cell lung cancer (NSCLC). J Clin Oncol 2015; (suppl): abstr 8006 33
    PubMedGoogle Scholar
  • 27 Rizvi NA, Hellmann MD, Snyder A et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015; 348: 124-128
    CrossrefPubMedGoogle Scholar
  • 28 Sequist LV, Yang JC, Yamamoto N 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: 3327-3334
    CrossrefPubMedGoogle Scholar
  • 29 Sequist LV, Rolfe L, Allen AR. Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med 2015; 373: 1700-1709
    PubMedGoogle Scholar
  • 30 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
    CrossrefPubMedGoogle Scholar
  • 31 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
    CrossrefPubMedGoogle Scholar
  • 32 Shaw AT, Ou SH, Bang YJ et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med 2014; 371: 1963-1971
    CrossrefPubMedGoogle Scholar
  • 33 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
    CrossrefPubMedGoogle Scholar
  • 34 The Clinical Lung Cancer Genome Project (CLCGP), Network Genomic Medicine (NGM), 2013. A genomics-based classification of human lung tumors. Sci Transl Med 2013; 5: 209ra153
    PubMedGoogle Scholar
  • 35 Van Allen EM, Miao D, Schilling B et al. Genomic correlates of response to CTLA4 blockade in metastatic melanoma. Science 2015; 350: 207-211
    CrossrefPubMedGoogle Scholar
  • 36 Wu YL, Zhou C, Hu CP et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 2014; 15: 213-222
    CrossrefPubMedGoogle Scholar
  • 37 Yang JC, Sequist LV, Geater SL et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol 2015; 16: 830-838
    CrossrefPubMedGoogle Scholar
  • 38 Yu HA, Arcila ME, Rekhtman N et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 2013; 19: 2240-2247
    CrossrefPubMedGoogle Scholar
  • 39 Mok TSK, Wu Y, Nakagawa K et al. Gefitinib/chemotherapy vs chemotherapy in epidermal growth factor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) after progression on first-line gefitinib: the phase III, randomised IMPRESS study. Ann Oncol 2014; abstr LBA2_PR 25 (Suppl. 04)
    PubMedGoogle Scholar