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

BACKGROUND

Advanced non-small cell lung cancer (NSCLC) patients who harbor anaplastic lymphoma kinase () rearrangement are sensitive to an ALK inhibitor (crizotinib), but not all -positive patients benefit equally from crizotinib treatment. We analyze the impact of mutations on response to crizotinib in patients with rearrangement NSCLC.

METHODS

Sixty-six rearrangement NSCLC patients receiving crizotinib were analyzed. 21 cases were detected successfully by the next generation sequencing validation FFPE before crizotinib. 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

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 gene wild group and mutation group patients (P=0.038, P=0.021, respectively).

CONCLUSIONS

mutations reduce responsiveness to crizotinib and worsen prognosis in rearrangement NSCLC patients.