Huy Gia Vuong1,2, Thu Quynh Nguyen3, Hoang Cong Nguyen3, Phuoc Truong Nguyen3, An Thi Nhat Ho4, Lewis Hassell5. 1. Department of Pathology, Oklahoma University Health Sciences Center, Oklahoma City, OK, 73104, USA. huyvuong@hotmail.com. 2. Stephenson Cancer Center, Oklahoma University of Health Sciences Center, Oklahoma City, OK, 73104, USA. huyvuong@hotmail.com. 3. Faculty of Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, 700-000, Vietnam. 4. Department of Pulmonary and Critical Care Medicine, Saint Louis University, St. Louis, MO, 63104, USA. 5. Department of Pathology, Oklahoma University Health Sciences Center, Oklahoma City, OK, 73104, USA.
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.
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.
Authors: Ramaswamy Govindan; Charu Aggarwal; Scott J Antonia; Marianne Davies; Steven M Dubinett; Andrea Ferris; Patrick M Forde; Edward B Garon; Sarah B Goldberg; Raffit Hassan; Matthew D Hellmann; Fred R Hirsch; Melissa L Johnson; Shakun Malik; Daniel Morgensztern; Joel W Neal; Jyoti D Patel; David L Rimm; Sarah Sagorsky; Lawrence H Schwartz; Boris Sepesi; Roy S Herbst Journal: J Immunother Cancer Date: 2022-05 Impact factor: 12.469
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