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TP53 mutations predict for poor survival in ALK rearrangement lung adenocarcinoma patients treated with crizotinib
Wen-Xian Wang1, Chun-Wei Xu2, Yan-Ping Chen2
1Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou 310022, China.
Background:
Advanced non-small cell lung cancer (NSCLC) patients who harbor anaplastic lymphoma kinase (ALK) rearrangement are sensitive to an ALK inhibitor (crizotinib), but not all ALK-positive patients benefit equally from crizotinib treatment. We analyze the impact of TP53 mutations on response to crizotinib in patients with ALK rearrangement NSCLC.
Methods:
Sixty-six ALK rearrangement NSCLC patients receiving crizotinib were analyzed. 21 cases were detected successfully by the next generation sequencing validation FFPE before crizotinib. TP53 mutations were evaluated in 8 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).
Results:
TP53 mutations were observed in 2 (25.00%), 1 (12.50%), 1 (12.50%) and 4 (50.00%) patients in exons 5, 6, 7 and 8, respectively. The majority of patients were male (75.00%, 6/8), less than 65 years old (62.50%, 5/8) and never smokers (75.00%, 6/8). ORR and DCR for crizotinib in the entire case series were 61.90% and 71.43%, respectively. Statistically significant difference was observed in terms of PFS and OS between TP53 gene wild group and mutation group patients (P=0.038, P=0.021, respectively).
Conclusions:
TP53 mutations reduce responsiveness to crizotinib and worsen prognosis in ALK rearrangement NSCLC patients.
Insights
TP53 mutations in anaplastic lymphoma kinase (ALK) rearrangement non-small cell lung cancer (NSCLC) patients receiving crizotinib are linked to poorer outcomes. These mutations significantly reduce progression-free and overall survival, impacting treatment effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement shows sensitivity to ALK inhibitors like crizotinib.
- However, not all ALK-positive NSCLC patients respond equally to crizotinib, suggesting other genetic factors influence treatment efficacy.
Purpose of the Study:
- To investigate the impact of TP53 mutations on the response to crizotinib in patients with ALK-rearranged NSCLC.
- To evaluate how TP53 mutations affect clinical outcomes such as objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
Main Methods:
- Analysis of 66 ALK-rearrangement NSCLC patients treated with crizotinib.
- Next-generation sequencing was used for TP53 mutation detection in 21 cases, with detailed evaluation in 8 patients.
- Correlation of TP53 mutation status with DCR, ORR, PFS, and OS.
Main Results:
- TP53 mutations were identified in various exons, with a higher prevalence in exons 5 and 8.
- The majority of patients with TP53 mutations were male, under 65, and never-smokers.
- A statistically significant difference in PFS (P=0.038) and OS (P=0.021) was observed between patients with and without TP53 mutations.
Conclusions:
- TP53 mutations are associated with reduced responsiveness to crizotinib in ALK-rearranged NSCLC.
- The presence of TP53 mutations negatively impacts the prognosis of these patients, worsening both PFS and OS.
