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Favorable predictors for survival in advanced ALK-positive non-small cell lung cancer patients beyond crizotinib resistance

BACKGROUND:

Crizotinib has demonstrated favorable efficacy in patients with advanced ALK-positive non-small cell lung cancer (NSCLC). Unfortunately, the majority of ALK-positive patients ultimately develop acquired resistance within one year after the initiation of crizotinibtreatment; however, the estimation of overall survival (OS) beyond crizotinib resistance has not yet been fully demonstrated. The purpose of this study was to identify favorable predictors affecting survival outcome.

METHODS:

In this single-center retrospective study, the data of 136 patients with advanced ALK-positive NSCLC beyond crizotinib resistance were analyzed between January 2013 and December 2017. Patients were divided into two groups according to intracranial or extracranial progression on crizotinib, and sequential therapies including crizotinib continuation with local therapy, next-generation ALK inhibitors, and chemotherapy. The primary endpoint was the median OS duration from the start of crizotinib resistance to death or the last follow-up. Univariate and multivariate Cox analyses of OS were carried out.

RESULTS:

At the time of analysis, 60 (41.1%) of the 136 patients had died. Median progression free survival (PFS) and OS from the metastatic diagnosis were 10.4 and 41.3 months, respectively. Sequential therapies administered beyond crizotinib treatment were: next-generation ALK inhibitors (54 patients), chemotherapy (20 patients), and crizotinib continuation with local therapy (62 patients). Multivariate Cox analysis revealed that long PFS with crizotinib (≥ 10.4 months), intracranial progression, and next-generation ALK inhibitors were significantly associated with a decreased risk of death.

CONCLUSION:

Long PFS with crizotinib (≥10.4 months), intracranial progression, and use of next-generation ALK inhibitors might be favorable predictors for OS in advanced ALK-positive NSCLC patients.

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S1068 Crizotinib (PF-02341066) Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. It is also a potent ROS1 inhibitor with Ki value less than 0.025 nM. (103) (13)

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