Efficacy and Safety of Crizotinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with ROS1 Rearrangement or MET
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SYSTEMATIC REVIEW
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 Huy Gia Vuong1,2 · Thu Quynh Nguyen3 · Hoang Cong Nguyen3 · Phuoc Truong Nguyen3 · An Thi Nhat Ho4 · Lewis Hassell1
© Springer Nature Switzerland AG 2020
Abstract Background Crizotinib has been approved for the treatment of non-small-cell lung cancer (NSCLC) with ROS protooncogene 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.
1 Introduction Lung cancer continues to be the deadliest malignancy in the world. It caused 1.8 million deaths in 2018 and has a 5-year survival rate of only about 15% [1]. Lung cancer is classified into two types: small-cell and non-small-cell lung cancer (NSCLC). While the former accounts for 15% of lung cancers and is aggressive and mostly incurable at advanced stages, the latter accounts for about 85% of lung cancer and often has better prognosis because of its differing underlying biology.
* Huy Gia Vuong [email protected] Extended author information available on the last page of the article
Over the past several years, the emergence of genomics has led to the identification of specific driver mutations in NSCLC, which have become targets for more specific treatment [2–7]. Of those, the driver mutations of protein tyrosine kinase receptor MET encoded by gene MET, and tyrosine kinase receptor ROS proto-oncogene 1 (ROS1) encoded by gene ROS1
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