Predictive and Prognostic Potential of TP53 in Patients With Advanced Non-Small-Cell Lung Cancer Treated With EGFR-TKI: Analysis of a Phase III Randomized Clinical Trial (CTONG 0901)

Clin Lung Cancer. 2021 Mar;22(2):100-109.e3. doi: 10.1016/j.cllc.2020.11.001. Epub 2020 Nov 17.


Background: Mutations in TP53 are commonly found in patients with epidermal growth factor receptor (EGFR) mutant advanced non-small-cell lung cancer (NSCLC). In this study, we determined the predictive and prognostic potential of different subtypes of TP53 using data from a phase III randomized trial (CTONG 0901).

Patients and methods: The trial enrolled 195 patients who had undergone next-generation sequencing of 168 genes before treatment with EGFR tyrosine kinase inhibitors. Mutations in TP53 (exon 4 or 7, other mutations, and wild-type) were analyzed based on the therapeutic response and survival. A Cox proportional hazards model was used to determine the potential of the predictive and prognostic factors.

Results: All 195 patients harbored activating EGFR mutations: the most common concomitant mutations were TP53 (134/195, 68.7%), CTNNB1 (20/195, 10.3%), and RB1 (16/195, 8.2%). The genetic profiles between patient subgroups administered first-line (132, 67.7%) or later-line (63, 32.3%) treatments did not significantly differ. The median progression-free survival in patients with mutations in exon 4 or 7 of TP53, other TP53 mutations, and wild-type TP53 were 9.4, 11.0, and 14.5 months (P = .009), respectively. Overall survival times were 15.8, 20.0, and 26.1 months (P = .004), respectively. Mutations in exon 4 or 7 of TP53 served as independent prognostic factors for progression-free (P = .001) and overall survival (P = .004) in patients.

Conclusion: Mutations in exon 4 and/or 7 in TP53 are promising predictive and prognostic indicators in EGFR-mutated NSCLC.

Keywords: Mutation spectrum; Next-generation sequencing; Survival; TP53exon; Tyrosine kinase inhibitor.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Exons / genetics
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Survival Analysis
  • Tumor Suppressor Protein p53 / genetics*


  • Protein Kinase Inhibitors
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • EGFR protein, human
  • ErbB Receptors