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Effect of Coexisting KRAS and TP53 Mutations in Patients Treated With Chemotherapy for Non-small-cell Lung Cancer

Pascale Tomasini1, Celine Mascaux1, Kevin Jao2

  • 1Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network and Department of Medicine, University of Toronto, Toronto, ON, Canada; Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.

Clinical Lung Cancer
|February 17, 2019
PubMed
Abstract

Insights

Patients with non-small-cell lung cancer (NSCLC) and wild-type KRAS/TP53 mutations showed longer overall survival when receiving chemotherapy. This study validates findings that chemotherapy is not deleterious in NSCLC patients with coexisting KRAS/TP53 mutations.

Area of Science:

  • Oncology
  • Genetics
  • Cancer Research

Background:

  • KRAS and TP53 mutations are frequent in non-small-cell lung cancer (NSCLC).
  • Previous research suggested adjuvant chemotherapy might be harmful for NSCLC patients with coexisting KRAS/TP53 mutations.

Purpose of the Study:

  • To validate the impact of adjuvant chemotherapy on NSCLC patients with KRAS and TP53 mutations.
  • To analyze the correlation between KRAS/TP53 mutation status and clinical outcomes in NSCLC patients receiving chemotherapy.

Main Methods:

  • Retrospective analysis of 218 NSCLC patients tested for KRAS and TP53 mutations.
  • Mutation status determined via next-generation sequencing or multiplex assays.
  • Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) were primary and secondary endpoints.

Main Results:

  • No significant difference in DFS/PFS was observed between patients with coexisting KRAS/TP53 mutations and other groups across different chemotherapy regimens (adjuvant, chemoradiation, palliative).
  • Overall survival (OS) was significantly longer in patients with wild-type KRAS and TP53 (WT/WT) compared to those with KRAS, TP53, or double mutations.
  • No significant OS difference was found specifically for the coexisting KRAS/TP53 mutated group compared to other mutated groups.

Conclusions:

  • Chemotherapy did not show a significant difference in DFS/PFS based on KRAS/TP53 mutation status in NSCLC patients.
  • Patients with wild-type KRAS and TP53 NSCLC demonstrated improved overall survival when treated with chemotherapy compared to those with mutations in these genes.
Keywords:
ChemotherapyCoexisting mutationsKRASLung cancerTP53

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