Clinical Efficacy of Crizotinib for Patients with Anaplastic Lymphoma Kinase-positive Advanced Non-small-cell Lung Cancer_West China Medical Journal

Authors：

 SongLingling , LiuHongmei ,  HuangMeijuan , WangXianfeng , ZhangXinxing , RenLi , WangJin , PengFeng , WangYongsheng , LuYou

Department of Thoracic Oncology, Cancer Center, West China Hospital/Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

HuangMeijuan, Email: hmj107@163.com

Keywords：

Anaplastic lymphoma kinase; Non-small-cell lung cancer; Crizotinib; Adverse events

DOI：

10.7507/1002-0179.20160011

Video：

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Objective To explore the therapeutic efficacy of crizotinib for patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC). Methods We retrospectively analyzed the clinical data of 31 ALK-positive NSCLC patients who received crizotinib treatment between November 2012 and May 2014 in the Department of Thoracic Oncology of West China Hospital. The median age of the patients was 51 years old, and the percentage of male and female patients was 45.2% and 54.8%, respectively. Among them, 74.2% were non-smokers, 74.2% had an ECOG performance status of 0-2. Histologically, adenocarcinoma was the highest proportion of 96.8%, and one (3.2%) patient had large cell carcinoma. Fifteen (48.4%) ALK-positive patients were given crizotinib in the first-line setting, and 16 (51.6%) accepted crizotinib in the second-line and beyond. Results The objective response rate (ORR) of the patients treated with crizotinib was 61.3%, and the disease control rate (DCR) was 90.3%. The median progression-free survival (time) was 10.0 months [(95% CI (2.9, 17.0) months]. The difference of ORR and DCR between the patients given crizotinib in the first-line setting and the patients given crizotinib in the second-line or beyond was not statistically significant (P=0.716 and P=0.600, respectively). The most frequent treatment-related adverse events were increased aspartate aminotransferase/alanine aminotransferase (64.5%), nausea and vomiting (35.5%), leukopenia (16.7%), vision disorder (16.1%), edema (12.9%), and diarrhea (12.9%), and most toxicities were grade 1 and 2. Conclusion This study shows that crizotinib can increase the objective response rate and disease control rate, prolong progression-free survival time in patients with advanced ALK-positive non–small-cell lung cancer. Crizotinib has relative fewer side effects and can be tolerated by the patients.

Citation： SongLingling, LiuHongmei, HuangMeijuan, WangXianfeng, ZhangXinxing, RenLi, WangJin, PengFeng, WangYongsheng, LuYou. Clinical Efficacy of Crizotinib for Patients with Anaplastic Lymphoma Kinase-positive Advanced Non-small-cell Lung Cancer. West China Medical Journal, 2016, 31(1): 43-47. doi: 10.7507/1002-0179.20160011 Copy

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9.	Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer[J]. N Engl J Med, 2013, 368(25):2385-2394.
10.	Chung WS, Park MS, Shin SJ, et al. Response evaluation in patients with colorectal liver metastases:RECIST version. 1 versus modfiied CT criteria[J]. AJR Am J Roentgenol, 2012, 199(4):809-815.
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12.	Takahashi T, Sonobe M, Kobayashi MA, et al. Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene[J]. Ann Surg Oncol, 2010, 17(3):889-897.
13.	Rodig SJ, Mino-Kenudson M, Dacic S, et al. Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population[J]. Clin Cancer Res, 2009, 15(16):5216-5223.
14.	Yang JJ, Zhang XC, Su J, et al. Lung cancers with concomitant EGFR mutations and ALK rearrangements:diverse responses to EGFR-TKI and crizotinib in relation to diverse receptors phosphorylation[J]. Clin Cancer Res, 2014, 20(5):1383-1392.
15.	Zhao N, Zheng SY, Yang JJ, et al. Lung adenocarcinoma harboring concomitant EGFR mutation and EML4-ALK fusion that benefits from three kinds of tyrosine kinase inhibitors:a case report and literature review[J]. Clin Lung Cancer, 2015, 16(2):E5-E9.
16.	Cao Y, Xiao G, Qiu X, et al. Efficacy and safety of crizotinib among Chinese EML4-ALK-positive, advanced-stage non-small cell lung cancer patients[J]. PLoS One, 2014, 9(12):e114008.

1. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma[J]. N Engl J Med, 2009, 361(10):947-957.
2. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer[J]. Nature, 2007, 448(7153):561-566.
3. Casaluce F, Sgambato A, Maione P, et al. ALK inhibitors:a new targeted therapy in the treatment of advanced NSCLC[J]. Target Oncol, 2013, 8(1):55-67.
4. Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK[J]. J Clin Oncol, 2009, 27(26):4247-4253.
5. 刘标, 时姗姗, 王璇, 等. 2011年肺腺癌新分类在评估组织学类型与分子学改变相关性中的意义[J]. 中华病理学杂志, 2012, 41(8):505-510.
6. Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer[J]. N Engl J Med, 2014, 371(23):2167-2177.
7. Shaw AT. Phase Ⅲ trial shows crizotinib superior to single-agent chemotherapy for ALK-positive advanced NSCLC[EB/OL]. (2012-09-30)[2015-03-26]. http:www.esmo.org/conferences/Past-Conferences/ESMO-2012-Congress/Congress-News/Phass-Ⅲ-trial-shows-crizotinib-superior-to-single-agent-chemotherly-for-Alk-adoanced-NSCLS.
8. Crinò L, Kim G, Riely GJ, et al. Initial phase Ⅱ results with crizotinibin advanced ALK-positive non small cell lung cancer(NSCLC):PROFILE 1005[J]. J Clin Oncol, 2011, 29(Suppl):abstr 7514.
9. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer[J]. N Engl J Med, 2013, 368(25):2385-2394.
10. Chung WS, Park MS, Shin SJ, et al. Response evaluation in patients with colorectal liver metastases:RECIST version. 1 versus modfiied CT criteria[J]. AJR Am J Roentgenol, 2012, 199(4):809-815.
11. CALGB. CTCAE v 4.0:common terminology criteria for adverse events[EB/OL].[2016-01-11]. http://www.calgb.org/Public/meetings/presentations/2009/summer_group/cra_cont_ed/06a_CTCAE-Setser_062009.pdf.
12. Takahashi T, Sonobe M, Kobayashi MA, et al. Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene[J]. Ann Surg Oncol, 2010, 17(3):889-897.
13. Rodig SJ, Mino-Kenudson M, Dacic S, et al. Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population[J]. Clin Cancer Res, 2009, 15(16):5216-5223.
14. Yang JJ, Zhang XC, Su J, et al. Lung cancers with concomitant EGFR mutations and ALK rearrangements:diverse responses to EGFR-TKI and crizotinib in relation to diverse receptors phosphorylation[J]. Clin Cancer Res, 2014, 20(5):1383-1392.
15. Zhao N, Zheng SY, Yang JJ, et al. Lung adenocarcinoma harboring concomitant EGFR mutation and EML4-ALK fusion that benefits from three kinds of tyrosine kinase inhibitors:a case report and literature review[J]. Clin Lung Cancer, 2015, 16(2):E5-E9.
16. Cao Y, Xiao G, Qiu X, et al. Efficacy and safety of crizotinib among Chinese EML4-ALK-positive, advanced-stage non-small cell lung cancer patients[J]. PLoS One, 2014, 9(12):e114008.

West China Medical Journal

Clinical Efficacy of Crizotinib for Patients with Anaplastic Lymphoma Kinase-positive Advanced Non-small-cell Lung Cancer

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