The effects of ceritinib and alectinib on ALK-rearrangement non-small-cell lung cancer (NSCLC): a single-arm meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

HU Xin , ZHANG Huiyun , BIAN Nannan ,  FENG Guosheng

Capital Medicine University Affiliated Beijing Chaoyang Hospital, Beijing, 100020, P.R.China;

Corresponding author：

FENG Guosheng, Email: fengguoshengcyh@126.com

Keywords：

Ceritinib; Alectinib; Non-small-cell lung cancer (NSCLC); Meta-analysis; Single-arm

DOI：

10.7507/1672-2531.201803048

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

ObjectivesTo systematically evaluate the effects of second-generation ALK-inhibitors: Ceritinib and Alectinib on ALK⁺ NSCLC patients.MethodsPubMed, EMbase, The Cochrane Library, WanFang Data, ClinicalTrials.gov and VIP databases were systematically searched for clinical trials containing treatment of two principal second-generation ALK-inhibitors for ALK (+) NSCLC patients from inception to December 31^st, 2017. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias included in the studies. Stata 12.0 software was used for meta-analysis.ResultsEleven studies were included. Meta-analysis showed that the ORR of all was 57% (95%CI 0.48 to 0.66, P<0.001). The ORR of patients with Crizotinib-resistance was 51% (95%CI 0.44 to 0.57,P<0.001). The IDCR of patients who had brain metastases was 78% (95%CI 0.71 to 0.86,P<0.001).ConclusionsThe second-generation ALK-inhibitors has effect on ALK (+) NSCLC. Due to limitation of the included studies, more larger sample studies are required to verify above conclusions.

Citation： HU Xin, ZHANG Huiyun, BIAN Nannan, FENG Guosheng. The effects of ceritinib and alectinib on ALK-rearrangement non-small-cell lung cancer (NSCLC): a single-arm meta-analysis. Chinese Journal of Evidence-Based Medicine, 2018, 18(9): 918-923. doi: 10.7507/1672-2531.201803048 Copy

1.	Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med, 2010, 363(18): 1693-1703.
2.	Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med, 2014, 371(23): 2167-2177.
3.	Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol, 2008, 26(21): 3543-3551.
4.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin, 2016, 66(1): 7-30.
5.	Frampton JE. Crizotinib: a review of its use in the treatment of anaplastic lymphoma kinase-positive, advanced non-small cell lung cancer. Drugs, 2013, 73(18): 2031-2051.
6.	Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALKrearranged lung cancers. Sci Transl Med, 2012, 4(120): 120ra17.
7.	Ou SH, Janne PA, Bartlett CH, et al. Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC. Ann Oncol, 2014, 25(2): 415-422.
8.	Weickhardt AJ, Scheier B, Burke JM, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol, 2012, 7(12): 1807-1814.
9.	王以富, 穆帅, 张晓军. ALK阳性非小细胞肺癌靶向治疗药物研究进展. 现代药物与临床, 2016, 31(7): 1118-1124.
10.	王佩鑫, 李宏田, 刘建蒙. 无对照二分类资料的Meta分析方法及Stata实现. 循证医学, 2012, 12(1): 52-55.
11.	Kim DW, Mehra R, Tan DSW, et al. Intracranial and whole-body response of ceritinib in ALK inhibitor-naive and previously ALK inhibitor-treated patients with ALK-rearranged non-small-cell lung cancer (NSCLC): updated results from the phase 1, multicentre, open-label ASCEND-1 trial. Lancet Oncol, 2016, 17(4): 452.
12.	Crinò L, Ahn MJ, De Marinis F, et al. Multicenter phase II study of whole-body and intracranial activity with ceritinib in patients with ALK-rearranged non-small-cell lung cancer previously treated with chemotherapy and crizotinib: results from ASCEND-2. J Clin Oncol, 2016, 34(24): 2866-2873.
13.	Felip E, Orlov S, Park K, et al. Phase 2 study of ceritinib in ALKi-naive patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC): Whole body responses in the overall pt group and in pts with baseline brain metastases (BM). Ann Oncol, 2016, 27(suppl 6): vi416-vi454.
14.	Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med, 2014, 370(13): 1189-1197.
15.	Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet, 2017, 389(10072): 917-929.
16.	Shaw AT, Kim TM, Crinò L, et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol, 2017, 18(7): 874-886.
17.	Seto T, Kiura K, Nishio M, et al. CH5424802(RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study. Lancet Oncol, 2013, 14(7): 590-598.
18.	Ou SHI, Ahn JS, De Petris L, et al. Alectinib in crizotinib-refractory ALK-rearranged non-small-cell lung cancer: a phase II global study. J Clin Oncol, 2015, 34(7): 661-668.
19.	Shaw AT, Gandhi L, Gadgeel S, et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol, 2016, 17(2): 234-242.
20.	Gadgeel SM, Gandhi L, Riely GJ, et al. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol, 2014, 15(10): 1119-1128.
21.	Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med, 2017, 377(9): 829-838.
22.	Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med, 2013, 368(25): 2385-2394.
23.	Hamilton G, Rath B, Burghuber O. Pharmacokinetics of crizotinib in NSCLC patients. Expert Opin Drug Metab Toxicol, 2015, 11(5): 835-842.
24.	Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med, 2014, 371(23): 2167-2177.

1. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med, 2010, 363(18): 1693-1703.
2. Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med, 2014, 371(23): 2167-2177.
3. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol, 2008, 26(21): 3543-3551.
4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin, 2016, 66(1): 7-30.
5. Frampton JE. Crizotinib: a review of its use in the treatment of anaplastic lymphoma kinase-positive, advanced non-small cell lung cancer. Drugs, 2013, 73(18): 2031-2051.
6. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALKrearranged lung cancers. Sci Transl Med, 2012, 4(120): 120ra17.
7. Ou SH, Janne PA, Bartlett CH, et al. Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC. Ann Oncol, 2014, 25(2): 415-422.
8. Weickhardt AJ, Scheier B, Burke JM, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol, 2012, 7(12): 1807-1814.
9. 王以富, 穆帅, 张晓军. ALK阳性非小细胞肺癌靶向治疗药物研究进展. 现代药物与临床, 2016, 31(7): 1118-1124.
10. 王佩鑫, 李宏田, 刘建蒙. 无对照二分类资料的Meta分析方法及Stata实现. 循证医学, 2012, 12(1): 52-55.
11. Kim DW, Mehra R, Tan DSW, et al. Intracranial and whole-body response of ceritinib in ALK inhibitor-naive and previously ALK inhibitor-treated patients with ALK-rearranged non-small-cell lung cancer (NSCLC): updated results from the phase 1, multicentre, open-label ASCEND-1 trial. Lancet Oncol, 2016, 17(4): 452.
12. Crinò L, Ahn MJ, De Marinis F, et al. Multicenter phase II study of whole-body and intracranial activity with ceritinib in patients with ALK-rearranged non-small-cell lung cancer previously treated with chemotherapy and crizotinib: results from ASCEND-2. J Clin Oncol, 2016, 34(24): 2866-2873.
13. Felip E, Orlov S, Park K, et al. Phase 2 study of ceritinib in ALKi-naive patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC): Whole body responses in the overall pt group and in pts with baseline brain metastases (BM). Ann Oncol, 2016, 27(suppl 6): vi416-vi454.
14. Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med, 2014, 370(13): 1189-1197.
15. Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet, 2017, 389(10072): 917-929.
16. Shaw AT, Kim TM, Crinò L, et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol, 2017, 18(7): 874-886.
17. Seto T, Kiura K, Nishio M, et al. CH5424802(RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study. Lancet Oncol, 2013, 14(7): 590-598.
18. Ou SHI, Ahn JS, De Petris L, et al. Alectinib in crizotinib-refractory ALK-rearranged non-small-cell lung cancer: a phase II global study. J Clin Oncol, 2015, 34(7): 661-668.
19. Shaw AT, Gandhi L, Gadgeel S, et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol, 2016, 17(2): 234-242.
20. Gadgeel SM, Gandhi L, Riely GJ, et al. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol, 2014, 15(10): 1119-1128.
21. Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med, 2017, 377(9): 829-838.
22. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med, 2013, 368(25): 2385-2394.
23. Hamilton G, Rath B, Burghuber O. Pharmacokinetics of crizotinib in NSCLC patients. Expert Opin Drug Metab Toxicol, 2015, 11(5): 835-842.
24. Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med, 2014, 371(23): 2167-2177.

Previous Article
The application value of 6-minute walking test in clinical evaluation of chronic heart failure
Next Article
Hydrotalcite in the treatment of reflux esophagitis: a meta-analysis

Chinese Journal of Evidence-Based Medicine

The effects of ceritinib and alectinib on ALK-rearrangement non-small-cell lung cancer (NSCLC): a single-arm meta-analysis

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content