Anaplastic Lymphoma Kinase Variants and the Percentage of ALK-Positive Tumor Cells and the Efficacy of Crizotinib in Advanced NSCLC

作者：Lei, Yuan-Yuan; Yang, Jin-Ji; Zhang, Xu-Chao; Zhong, Wen-Zhao; Zhou, Qing; Tu, Hai-Yan; Tian, Hong-Xia; Guo, Wei-Bang; Yang, Lu-Lu; Yan, Hong-Hong; Chen, Hua-Jun; Xie, Zhi; Su, Jian; Han, Jie-Fei; Wu, Yi-Long^*

来源：Clinical Lung Cancer, 2016, 17(3): 223-231.

DOI：10.1016/j.cllc.2015.09.002

• Anaplastic lymphoma kinase variants
• Crizotinib
• Non-small-cell lung cancer
• Percentage of ALK-positive cells
• Progression-free survival

Advanced nonesmall-cell lung cancer 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. Our analysis showed that ALK variants might have no correlation with clinical response to crizotinib, and the percentage of ALK-positive cells might correlate with the extent of benefit from crizotinib treatment.
Background: Anaplastic lymphoma kinase (ALK)-positive nonesmall-cell lung cancer patients exhibited heterogeneous magnitude of response and duration time to criztotinib treatment. This study explored ALK variants and the percentage of ALK-positive cells using fluorescent in situ hybridization (FISH) on clinical efficacy of crizotinib. Patients and Methods: A total of 120 patients with ALK rearrangement who were treated with criztotinib were enrolled. ALK variants were clarified in 61 patients, and ALK percentages were evaluated using FISH in 114 ALK-positive patients. Retrospectively, objective response rate, and progression-free survival (PFS) were evaluated. Results: A total of 61 patients with specific ALK variants were divided into 3 subgroups, echinoderm microtubule-associated protein like 4 (EML4)-ALK variant 1 (n = 22), EML4-ALK variant 3a/b (n = 18), and other ALK variants (n = 21). Median PFS in the 3 subgroups was 11.0 months (95% confidence interval [CI], 5.5-16.5), 10.9 months (95% CI, 5.9-15.8), 7.4 months (95% CI, 3.2-11.6), respectively, and no significant difference (P = .795) existed among them. The percentage of ALKpositive cells in FISH analysis was weakly correlated with PFS (r(s) = 0.235; P = .015). Additionally, it was also weakly correlated with best response to crizotinib (r(s) = 0.288; P = .003). Overall, there were 45, 49, and 26 patients receiving first, second, and third or further-line crizotinib, respectively. Median PFS in the first-line setting (10.5 months; 95% CI, 8.6-12.4) was significantly longer than that in the second-line setting (8.3 months; 95% CI, 4.7-12.0; P = .020). Conclusion: Anaplastic lymphoma kinase variants might have no correlation with clinical response to crizotinib. The percentage of ALK-positive cells might correlate with the extent of benefit from crizotinib treatment.

• 出版日期2016-5
• 单位广东省人民医院