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Detection of TP53 mutations in tissue or liquid rebiopsies at progression identifies ALK+ lung cancer patients with poor survival

Anaplastic lymphoma kinase (ALK) sequencing can identify resistance mechanisms and guide next-line therapy in ALK+ non-small-cell lung cancer (NSCLC), but the clinical significance of other rebiopsy findings remains unclear. We analysed all stage-IV ALK+ NSCLC patients with longitudinally assessable...

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Main Authors: Christopoulos, Petros (Author) , Dietz, Steffen (Author) , Kirchner, Martina (Author) , Volckmar, Anna-Lena (Author) , Endris, Volker (Author) , Neumann, Olaf (Author) , Heußel, Claus Peter (Author) , Herth, Felix (Author) , Eichhorn, Martin E. (Author) , Meister, Michael (Author) , Budczies, Jan (Author) , Allgäuer, Michael (Author) , Leichsenring, Jonas (Author) , Bischoff, Helge (Author) , Schirmacher, Peter (Author) , Thomas, Michael (Author) , Sültmann, Holger (Author) , Stenzinger, Albrecht (Author)
Format: Article (Journal)
Language:English
Published: 21 January 2019
In: Cancers
Year: 2019, Volume: 11, Issue: 1
ISSN:2072-6694
DOI:10.3390/cancers11010124
Online Access:Verlag, Volltext: https://doi.org/10.3390/cancers11010124
Verlag, Volltext: https://www.mdpi.com/2072-6694/11/1/124
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Author Notes:Petros Christopoulos, Steffen Dietz, Martina Kirchner, Anna-Lena Volckmar, Volker Endris, Olaf Neumann, Simon Ogrodnik, Claus-Peter Heussel, Felix J. Herth, Martin Eichhorn, Michael Meister, Jan Budczies, Michael Allgäuer, Jonas Leichsenring, Tomasz Zemojtel, Helge Bischoff, Peter Schirmacher, Michael Thomas, Holger Sültmann, Albrecht Stenzinger
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Summary:Anaplastic lymphoma kinase (ALK) sequencing can identify resistance mechanisms and guide next-line therapy in ALK+ non-small-cell lung cancer (NSCLC), but the clinical significance of other rebiopsy findings remains unclear. We analysed all stage-IV ALK+ NSCLC patients with longitudinally assessable TP53 status treated in our institutions (n = 62). Patients with TP53 mutations at baseline (TP53mutbas, n = 23) had worse overall survival (OS) than patients with initially wild-type tumours (TP53wtbas, n = 39, 44 vs. 62 months in median, p = 0.018). Within the generally favourable TP53wtbas group, detection of TP53 mutations at progression defined a “converted” subgroup (TP53mutconv, n = 9) with inferior OS, similar to that of TP53mutbas and shorter than that of patients remaining TP53 wild-type (TP53wtprogr, 45 vs. 94 months, p = 0.043). Progression-free survival (PFS) under treatment with tyrosine kinase inhibitors (TKI) for TP53mutconv was comparable to that of TP53mutbas and also shorter than that of TP53wtprogr cases (5 and 8 vs. 13 months, p = 0.0039). Fewer TP53wtprogr than TP53mutbas or TP53mutconv cases presented with metastatic disease at diagnosis (67% vs. 91% or 100%, p < 0.05). Thus, acquisition of TP53 mutations at progression is associated with more aggressive disease, shorter TKI responses and inferior OS in ALK+ NSCLC, comparable to primary TP53 mutated cases.
Item Description:Gesehen am 26.06.2019
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Physical Description:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers11010124

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