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Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer.
Kron, A; Alidousty, C; Scheffler, M; Merkelbach-Bruse, S; Seidel, D; Riedel, R; Ihle, M A; Michels, S; Nogova, L; Fassunke, J; Heydt, C; Kron, F; Ueckeroth, F; Serke, M; Krüger, S; Grohe, C; Koschel, D; Benedikter, J; Kaminsky, B; Schaaf, B; Braess, J; Sebastian, M; Kambartel, K-O; Thomas, R; Zander, T; Schultheis, A M; Büttner, R; Wolf, J.
Afiliação
  • Kron A; Network Genomic Medicine, Cologne, Germany; Lung Cancer Group Cologne, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany.
  • Alidousty C; Network Genomic Medicine, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
  • Scheffler M; Network Genomic Medicine, Cologne, Germany; Lung Cancer Group Cologne, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany.
  • Merkelbach-Bruse S; Network Genomic Medicine, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
  • Seidel D; Center for Integrated Oncology Köln Bonn, Cologne, Germany; CECAD Cluster of Excellence, University of Cologne, Cologne, Germany.
  • Riedel R; Network Genomic Medicine, Cologne, Germany; Lung Cancer Group Cologne, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany.
  • Ihle MA; Network Genomic Medicine, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
  • Michels S; Network Genomic Medicine, Cologne, Germany; Lung Cancer Group Cologne, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany.
  • Nogova L; Network Genomic Medicine, Cologne, Germany; Lung Cancer Group Cologne, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany.
  • Fassunke J; Network Genomic Medicine, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
  • Heydt C; Network Genomic Medicine, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
  • Kron F; Network Genomic Medicine, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany.
  • Ueckeroth F; Network Genomic Medicine, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
  • Serke M; Network Genomic Medicine, Cologne, Germany; Department of Pneumology, Lungenklinik Hemer des Deutschen Gemeinschafts-Diakonieverbandes GmbH, Hemer, Germany.
  • Krüger S; Network Genomic Medicine, Cologne, Germany; Department of Pneumology, Florence Nightingale Hospital, Düsseldorf, Germany.
  • Grohe C; Network Genomic Medicine, Cologne, Germany; Department of Pneumology, Evangelische Lungenklinik Berlin (Paul Gerhardt Diakonie), Berlin, Germany.
  • Koschel D; Network Genomic Medicine, Cologne, Germany; Department of Pneumology, Fachkrankenhaus Coswig, Coswig, Germany.
  • Benedikter J; Network Genomic Medicine, Cologne, Germany; Department of Pneumology, Klinikum Bogenhausen, Munich, Germany.
  • Kaminsky B; Network Genomic Medicine, Cologne, Germany; Department of Pneumology, Krankenhaus Bethanien, Solingen, Germany.
  • Schaaf B; Network Genomic Medicine, Cologne, Germany; Lung Cancer Center, Klinikum Dortmund GmbH, Dortmund, Germany.
  • Braess J; Network Genomic Medicine, Cologne, Germany; Department of Oncology and Hematology, Krankenhaus Barmherzige Brueder, Regensburg, Germany.
  • Sebastian M; Network Genomic Medicine, Cologne, Germany; Department of Oncology and Hematology, University Hospital Frankfurt (Johannes-Wolfgang Goethe Institute), Frankfurt am Main, Germany.
  • Kambartel KO; Network Genomic Medicine, Cologne, Germany; Department of Pneumology, Bethanien Hospital Moers-Lungenzentrum, Moers, Germany.
  • Thomas R; Network Genomic Medicine, Cologne, Germany; Cologne Center for Genomics, University Hospital of Cologne, Cologne, Germany.
  • Zander T; Network Genomic Medicine, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany.
  • Schultheis AM; Network Genomic Medicine, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
  • Büttner R; Network Genomic Medicine, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
  • Wolf J; Network Genomic Medicine, Cologne, Germany; Lung Cancer Group Cologne, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany. Electronic address: juergen.wolf@uk-koeln.de.
Ann Oncol ; 29(10): 2068-2075, 2018 10 01.
Article em En | MEDLINE | ID: mdl-30165392
Background: We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC). Patients and methods: ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results: Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4-5.6) versus 10.3 months (95% CI: 8.6-12.0), P < 0.001; OS 15.0 months (95% CI: 5.0-24.9) versus 50.0 months (95% CI: 22.9-77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3-4.1) versus 6.2 months (95% CI: 1.8-10.5), P = 0.021; OS 2.0 months (95% CI: 0.0-4.6) versus 9.0 months (95% CI: 6.1-11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9-7.2) versus 14.0 months (95% CI: 8.0-20.1), P < 0.001; OS 17.0 months (95% CI: 6.7-27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1-10.7) versus 9.9 months (95% CI: 6.4-13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions: In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Rearranjo Gênico / Protocolos de Quimioterapia Combinada Antineoplásica / Proteína Supressora de Tumor p53 / Carcinoma Pulmonar de Células não Pequenas / Quinase do Linfoma Anaplásico / Neoplasias Pulmonares / Mutação Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Rearranjo Gênico / Protocolos de Quimioterapia Combinada Antineoplásica / Proteína Supressora de Tumor p53 / Carcinoma Pulmonar de Células não Pequenas / Quinase do Linfoma Anaplásico / Neoplasias Pulmonares / Mutação Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article