TP53 mutations predict for poor survival in ALK rearrangement lung adenocarcinoma patients treated with crizotinib

Wen-Xian Wang, Chun-Wei Xu, Yan-Ping Chen, Wei Liu, Li-Hua Zhong, Fang-Fang Chen, Wu Zhuang, Yun-Jian Huang, Zhang-Zhou Huang, Rong-Rong Chen, Yan-Fang Guan, Xin Yi, Tang- Feng Lv, Wei-Feng Zhu, Jian-Ping Lu, Xiao-Jiang Wang, Yi Shi, Xian-Dong Lin, Gang Chen, Yong Song


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.