Top

Published in:

01-06-2019 | NSCLC | Original Research Article

Efficacy of Crizotinib for Advanced ALK-Rearranged Non-Small-Cell Lung Cancer Patients with Brain Metastasis: A Multicenter, Retrospective Study in China

Authors: Puyuan Xing, Shouzheng Wang, Qiang Wang, Di Ma, Xuezhi Hao, Mengzhao Wang, Yan Wang, Li Shan, Tao Xin, Li Liang, Hongge Liang, Yang Du, Zhaohui Zhang, Junling Li

Published in: Targeted Oncology | Issue 3/2019

Abstract

Background

The efficacy of crizotinib for anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) patients with brain metastasis is controversial. Real-world research data are needed as further evidence.

Objective

We conducted a multicenter, retrospective study to explore how crizotinib affects the control of brain metastasis and the survival outcomes among Chinese patients.

Patients and Methods

We reviewed the medical records of unselected ALK-rearranged NSCLC patients treated with crizotinib at five hospitals in China from January 1, 2013 to November 30, 2017. Patients developing brain metastasis either before or during crizotinib treatment were included. Survival outcomes were analyzed by the Kaplan–Meier method, and prognostic factors were analyzed by multivariate Cox regression.

Results

A total of 174 patients were included in the analysis; 95 of these patients had baseline brain metastasis, while 79 patients developed brain metastasis during crizotinib treatment. Among patients with baseline brain metastasis, the median intracranial time to progression was 19.3 months (95% confidence interval [CI] 12.5–26.2) and the median overall survival (OS) was 53.4 months (95% CI not reached). A total of 135 patients experienced intracranial progression, and 94 of these patients continued crizotinib beyond progressive disease (CBPD). There was no significant difference in the median OS between patients with CBPD and without CBPD (48.3 months vs 53.4 months; p = 0.296).

Conclusions

ALK-rearranged advanced NSCLC patients with baseline brain metastasis can still achieve OS benefits from crizotinib treatment. However, patients with intracranial progression may not obtain a long-term survival benefit from continuation of CBPD.

The National Comprehensive Cancer Network (NCCN): Clinical Practice Guidelines in Oncology: non-small cell lung cancer, 2018; version 3. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp-nscl.

Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. New Engl J Med. 2010;363(18):1693–703. https://doi.org/10.1056/NEJMoa1006448.CrossRefPubMed

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 Clin Oncol. 2009;27(26):4247–53. https://doi.org/10.1200/jco.2009.22.6993.CrossRefPubMedPubMedCentral

Sun JM, Lira M, Pandya K, et al. Clinical characteristics associated with ALK rearrangements in never-smokers with pulmonary adenocarcinoma. Lung Cancer (Amsterdam, Netherlands). 2014;83(2):259–64. https://doi.org/10.1016/j.lungcan.2013.11.009.CrossRef

Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. New Engl J Med. 2014;371(23):2167–77. https://doi.org/10.1056/NEJMoa1408440.CrossRefPubMed

Solomon BJ, Kim DW, Wu YL, et al. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small-cell lung cancer. J Clin Oncol. 2018;36(22):2251–8. https://doi.org/10.1200/jco.2017.77.4794.CrossRefPubMed

Wu YL, Lu S, Lu Y, et al. Results of PROFILE 1029, a phase III comparison of first-line crizotinib versus chemotherapy in East Asian patients with ALK-positive advanced non-small cell lung cancer. J Thor Oncol. 2018;13(10):1539–48. https://doi.org/10.1016/j.jtho.2018.06.012.CrossRef

Dagogo-Jack I, Gill CM, Cahill DP, Santagata S, Brastianos PK. Treatment of brain metastases in the modern genomic era. Pharmacol Ther. 2017;170:64–72. https://doi.org/10.1016/j.pharmthera.2016.10.011.CrossRefPubMed

Costa DB, Shaw AT, Ou SH, et al. Clinical experience with crizotinib in patients with advanced ALK-rearranged non-small-cell lung cancer and brain metastases. J Clin Oncol. 2015;33(17):1881–8. https://doi.org/10.1200/jco.2014.59.0539.CrossRefPubMedPubMedCentral

10.

Wardak Z, Choy H. Improving treatment options for brain metastases from ALK-positive non-small-cell lung cancer. J Clin Oncol. 2016;34(34):4064–5. https://doi.org/10.1200/jco.2016.69.9587.CrossRefPubMed

11.

Rusthoven CG, Doebele RC. Management of brain metastases in ALK-positive non-small-cell lung cancer. J Clin Oncol. 2016;34(24):2814–9. https://doi.org/10.1200/jco.2016.67.2410.CrossRef

12.

Costa DB, Kobayashi S, Pandya SS, et al. CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib. J Clin Oncol. 2011;29(15):e443–5. https://doi.org/10.1200/jco.2010.34.1313.CrossRef

13.

Camidge DR, Peters S, Mok T, et al. Updated efficacy and safety data from the global phase III ALEX study of alectinib (ALC) vs crizotinib (CZ) in untreated advanced ALK + NSCLC. J Clin Oncol. 2018;36(suppl): abstr 9043.

14.

Gadgeel S, Peters S, Mok T, et al. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK +) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol. 2018;29(11):2214–22. https://doi.org/10.1093/annonc/mdy405.CrossRefPubMedPubMedCentral

15.

Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. New Engl J Med. 2018;379(21):2027–39. https://doi.org/10.1056/NEJMoa1810171.CrossRefPubMed

16.

Solomon BJ, Cappuzzo F, Felip E, et al. Intracranial efficacy of crizotinib versus chemotherapy in patients with advanced ALK-positive non-small-cell lung cancer: results from PROFILE 1014. J Clin Oncol. 2016;34(24):2858–65. https://doi.org/10.1200/jco.2015.63.5888.CrossRefPubMed

17.

Pacheco JM, Gao D, Smith D, et al. Natural history and factors associated with overall survival in stage IV ALK-rearranged non-small cell lung cancer. J Thorac Oncol. 2019;14(4):691–700. https://doi.org/10.1016/j.jtho.2018.12.014.CrossRefPubMed

Title: Efficacy of Crizotinib for Advanced ALK-Rearranged Non-Small-Cell Lung Cancer Patients with Brain Metastasis: A Multicenter, Retrospective Study in China
Authors: Puyuan Xing
Shouzheng Wang
Qiang Wang
Di Ma
Xuezhi Hao
Mengzhao Wang
Yan Wang
Li Shan
Tao Xin
Li Liang
Hongge Liang
Yang Du
Zhaohui Zhang
Junling Li
Publication date: 01-06-2019
Publisher: Springer International Publishing
Keywords: NSCLC
Lung Cancer
Metastasis
Lung Cancer
NSCLC
Lung Cancer
Crizotinib
Published in: Targeted Oncology / Issue 3/2019
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-019-00637-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Objective

Patients and Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2019

Crizotinib in Chinese Patients with ROS1-Rearranged Advanced Non‒Small-Cell Lung Cancer in Routine Clinical Practice

Real-Life Efficacy of Osimertinib in Pretreated Octogenarian Patients with T790M-Mutated Advanced Non-small Cell Lung Cancer

Comparison of Standard Initial Dose and Reduced Initial Dose Regorafenib for Colorectal Cancer Patients: A Retrospective Cohort Study

The Urinary Microbiome and Anticancer Immunotherapy: The Potentially Hidden Role of Unculturable Microbes

MINOAS: A Single-arm Translational Phase II Trial of FOLFIRI Plus Aflibercept as First-line Therapy in Unresectable, Metastatic Colorectal Cancer

Current Systemic Treatment Landscape of Advanced Gynecologic Malignancies

Keynote webinar | Spotlight on antibody–drug conjugates in cancer