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Predicting the Role of DNA Polymerase β Alone or with KRAS Mutations in Advanced NSCLC Patients Receiving Platinum-Based Chemotherapy.

Authors
  • Alvisi, Maria Francesca1
  • Ganzinelli, Monica2
  • Linardou, Helena3
  • Caiola, Elisa4
  • Lo Russo, Giuseppe2
  • Cecere, Fabiana Letizia5
  • Bettini, Anna Cecilia6
  • Psyrri, Amanda7
  • Milella, Michele8
  • Rulli, Eliana1
  • Fabbri, Alessandra9
  • De Maglie, Marcella10, 11
  • Romanelli, Pierpaolo10, 11
  • Murray, Samuel12
  • Ndembe, Gloriana4
  • Broggini, Massimo4
  • Garassino, Marina Chiara2
  • Marabese, Mirko4
  • 1 Laboratory of Methodology for Clinical Research, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy. , (Italy)
  • 2 Unit of Thoracic Oncology, Medical Oncology Department 1, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. , (Italy)
  • 3 4th Oncology Department, Metropolitan Hospital, 18547 Athens, Greece. , (Greece)
  • 4 Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy. , (Italy)
  • 5 Division of Medical Oncology 1, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy. , (Italy)
  • 6 UO Oncologia Medica, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy. , (Italy)
  • 7 Section of Oncology, Department of Internal Medicine, Attikon Hospital, National Kapodistrian University of Athens, 12462 Athens, Greece. , (Greece)
  • 8 Department of Medicine, Section of Medical Oncology, University and Hospital Trust of Verona, 37126 Verona, Italy. , (Italy)
  • 9 Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. , (Italy)
  • 10 Mouse & Animal Pathology Lab, Fondazione Filarete, 20139 Milan, Italy. , (Italy)
  • 11 Department of Veterinary Medicine, University of Milan, 20122 Milan, Italy. , (Italy)
  • 12 Biomarker Solutions Ltd., London EC1V 2NX, UK.
Type
Published Article
Journal
Journal of Clinical Medicine
Publisher
MDPI AG
Publication Date
Jul 30, 2020
Volume
9
Issue
8
Identifiers
DOI: 10.3390/jcm9082438
PMID: 32751518
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Clinical data suggest that only a subgroup of non-small cell lung cancer (NSCLC) patients has long-term benefits after front-line platinum-based therapy. We prospectively investigate whether KRAS status and DNA polymerase β expression could help identify patients responding to platinum compounds. Prospectively enrolled, advanced NSCLC patients treated with a first-line regimen containing platinum were genotyped for KRAS and centrally evaluated for DNA polymerase β expression. Overall survival (OS), progression-free survival (PFS), and the objective response rate (ORR) were recorded. Patients with KRAS mutations had worse OS (hazard ratio (HR): 1.37, 95% confidence interval (95% CI): 0.70-2.27). Negative DNA polymerase β staining identified a subgroup with worse OS than patients expressing the protein (HR: 1.43, 95% CI: 0.57-3.57). The addition of KRAS to the analyses further worsened the prognosis of patients with negative DNA polymerase β staining (HR: 1.67, 95% CI: 0.52-5.56). DNA polymerase β did not influence PFS and ORR. KRAS may have a negative role in platinum-based therapy responses in NSCLC, but its impact is limited. DNA polymerase β, when not expressed, might indicate a group of patients with poor outcomes. KRAS mutations in tumors not expressing DNA polymerase β further worsens survival. Therefore, these two biomarkers together might well identify patients for whom alternatives to platinum-based chemotherapy should be used.

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