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Updated: Jan 28, 2026

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Concomitant TP53 mutations with response to crizotinib treatment in patients with ALK-rearranged non-small-cell lung
Peng Song1, Fanshuang Zhang2, Yan Li2
1Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
TP53 mutations are the most prevalent mutations detected in non-small-cell lung cancer (NSCLC) and have been revealed as a negative prognostic biomarker of outcome. The impact of concomitant TP53 mutations in ALK-rearranged NSCLC remains uncertain.
Methods:
Tumor samples from 64 ALK-rearranged NSCLC patients receiving crizotinib treatment were subjected to next-generation sequencing (NGS) to identify TP53 mutational status. The clinicopathologic features of the TP53 mutations and its impact on the effect of crizotinib treatment were analyzed.
Results:
Among the 64 ALK-rearranged patients, 15 (23.4%) patients showed a TP53 mutation. Of these, six cases had disruptive mutations and nine with nondisruptive mutations. The objective response rate (ORR) and disease control rate (DCR) for TP53 mutated patients were both significantly lower compared with those for TP53 wild-type patients (p = 0.003 and 0.023, respectively). A significantly shorter progression-free survival (PFS) was found in TP53 mutated patients compared with TP53 wild-type patients (p = 0.045). Nondisruptive TP53 mutations were associated with a shorter PFS in comparison with disruptive TP53 mutations in ALK-rearranged patients (p = 0.069). When nondisruptive TP53 mutated patients were in comparison with TP53 wild-type patients, nondisruptive TP53 mutations were associated with a significant reduced PFS (p = 0.003).
Conclusions:
TP53 mutations, especially nondisruptive mutations, negatively affected the response to crizotinib and correlated with shorter PFS in ALK-rearranged NSCLC patients.
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