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- Title
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).
- Authors
Li, Xiang-Meng; Li, Wen-Feng; Lin, Jun-Tao; Yan, Hong-Hong; Tu, Hai-Yan; Chen, Hua-Jun; Wang, Bin-Chao; Wang, Zhen; Zhou, Qing; Zhang, Xu-Chao; Su, Jian; Chen, Rui-Lian; Wu, Yi-Long; Yang, Jin-Ji
- Abstract
<bold>Background: </bold>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).<bold>Patients and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>Mutations in exon 4 and/or 7 in TP53 are promising predictive and prognostic indicators in EGFR-mutated NSCLC.
- Subjects
LUNG cancer; PROTEINS; RESEARCH; SEQUENCE analysis; GENETIC mutation; PROTEIN kinase inhibitors; RESEARCH methodology; LUNG tumors; CELL receptors; PROGNOSIS; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; GENES; SURVIVAL analysis (Biometry)
- Publication
Clinical Lung Cancer, 2021, Vol 22, Issue 2, p100
- ISSN
1525-7304
- Publication type
journal article
- DOI
10.1016/j.cllc.2020.11.001