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

Wang WX1, Xu CW2, Chen YP2, Liu W2, Zhong LH2, Chen FF2, Zhuang W3, Huang YJ3, Huang ZZ3, Chen RR4, Guan YF4, Yi X4, Lv TF5, Zhu WF2, Lu JP2, Wang XJ2, Shi Y2, Lin XD2, Chen G2, Song Y5.

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Abstract

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).