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Efficacy and Safety of Crizotinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with ROS1 Rearrangement or MET Alteration: A Systematic Review and Meta-Analysis

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Abstract

Background

Crizotinib has been approved for the treatment of non-small-cell lung cancer (NSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion. This drug has also been granted breakthrough designation for NSCLCs with MET exon 14 alterations.

Objective

This systematic review and meta-analysis aimed to investigate the efficacy and safety of crizotinib in patients with these diseases.

Methods

We searched PubMed and Web of Science for relevant studies. Meta-analysis of proportions was conducted to calculate the pooled rate of complete response, partial response, stable disease, progressive disease, disease control rate (DCR), objective response rate (ORR), and drug adverse effects (AEs) of crizotinib in NSCLCs with ROS1 rearrangement or MET alterations.

Results

A total of 20 studies were included for meta-analysis. Among patients with ROS1-positive NSCLC, crizotinib exhibited a pooled DCR of 93.2% (95% confidence interval [CI] 90.8–95.5) and a pooled ORR of 77.4% (95% CI 72.8–82.1). The median progression-free survival (PFS) and overall survival (OS) of patients in this group was 14.5 and 32.6 months, respectively. For NSCLC with MET alterations, crizotinib was associated with a lower efficacy (DCR 78.9% [95% CI 70.3–87.4] and ORR 40.6% [95% CI 28.3–53.0]). The median PFS was 5.2 months, and median OS was 12.7 months. The most common drug AEs were vision impairment (43.7%), edema (42.9%), and fatigue (40.1%).

Conclusion

Our study highlighted and confirmed the efficacy of crizotinib in patients with NSCLC with ROS1 or MET genetic alterations. Crizotinib had remarkable effects on advanced NSCLC with ROS1 fusion, as previously reported. However, the role of this targeted therapy in MET-altered NSCLC remains investigational.

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Acknowledgements

The authors thank Dr. Michael Magguilli (Oklahoma University Health Sciences Center) for his helpful advice that improved this paper.

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Authors and Affiliations

  1. Department of Pathology, Oklahoma University Health Sciences Center, Oklahoma City, OK, 73104, USA

    Huy Gia Vuong & Lewis Hassell

  2. Stephenson Cancer Center, Oklahoma University of Health Sciences Center, Oklahoma City, OK, 73104, USA

    Huy Gia Vuong

  3. Faculty of Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, 700-000, Vietnam

    Thu Quynh Nguyen, Hoang Cong Nguyen & Phuoc Truong Nguyen

  4. Department of Pulmonary and Critical Care Medicine, Saint Louis University, St. Louis, MO, 63104, USA

    An Thi Nhat Ho

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Contributions

HGV contributed to the study conceptualization, data curation, formal analysis, investigation, methodology, project administration, software, validation, supervision, writing-review, and editing. TQN contributed to the data curation, formal analysis, investigation, software, supervision, writing-review, and editing. HCN contributed to the data curation, formal analysis, investigation, validation, supervision, writing-review, and editing. PTN and ATNH contributed to the data curation, formal analysis, investigation, software, methodology, validation, supervision, writing-review, and editing. LH contributed to the data curation, formal analysis, investigation, software, methodology, project administration, validation, supervision, writing-review, and editing.

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Vuong, H.G., Nguyen, T.Q., Nguyen, H.C. et al. Efficacy and Safety of Crizotinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with ROS1 Rearrangement or MET Alteration: A Systematic Review and Meta-Analysis. Targ Oncol 15, 589–598 (2020). https://doi.org/10.1007/s11523-020-00745-7

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