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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-04-11

AUTHORS

Chang Liu, Hui Yu, Jianhua Chang, Haiquan Chen, Yuan Li, Weixin Zhao, Kuaile Zhao, Zhengfei Zhu, Si Sun, Min Fan, Jialei Wang

ABSTRACT

BackgroundApproximately 1–2% of patients with non‒small-cell lung cancer (NSCLC) harbor ROS1 rearrangements. Crizotinib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets anaplastic lymphoma kinase (ALK), MET, and ROS1, has shown marked antitumor activity in patients with ROS1-positive advanced NSCLC.ObjectiveOur objective was to analyze the efficacy and safety of crizotinib treatment in Chinese patients with advanced NSCLC with ROS1 rearrangement in real-world clinical practice.MethodsWe included 35 patients with ROS1-positive NSCLC in this retrospective analysis. All received crizotinib 250 mg twice daily between March 2016 and April 2018 at the Fudan University Shanghai Cancer Center. All had histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangements, which were identified by fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, or next-generation sequencing. The main outcome measures were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events.ResultsThe median age of the patients was 51.0 years; 23 (65.7%) were female and 28 (80.0%) were never smokers. All were diagnosed as having adenocarcinoma; eight patients (22.9%) had brain metastases at baseline. The ORR and DCR were 71.4% and 94.3%, respectively. The estimated median PFS was 11.0 months (95% confidence interval [CI] 7.8–14.2). The estimated median OS was 41.0 months (95% CI 22.5–59.5). Elevated transaminases (54.3%), vision disorder (25.7%), elevated blood creatinine (22.9%), diarrhea (20.0%), and vomiting (20.0%) were the most commonly reported adverse effects.ConclusionCrizotinib was effective and well tolerated in Chinese patients with ROS1-positive advanced NSCLC in real-world clinical practice. The progression sites and patterns, as well as treatments after first disease progression on crizotinib were diverse. Crizotinib beyond progressive disease and local therapy after failure of crizotinib treatment were feasible and effective in clinical practice. More... »

PAGES

315-323

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11523-019-00636-6

DOI

http://dx.doi.org/10.1007/s11523-019-00636-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113378585

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30976989


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29 schema:description BackgroundApproximately 1–2% of patients with non‒small-cell lung cancer (NSCLC) harbor ROS1 rearrangements. Crizotinib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets anaplastic lymphoma kinase (ALK), MET, and ROS1, has shown marked antitumor activity in patients with ROS1-positive advanced NSCLC.ObjectiveOur objective was to analyze the efficacy and safety of crizotinib treatment in Chinese patients with advanced NSCLC with ROS1 rearrangement in real-world clinical practice.MethodsWe included 35 patients with ROS1-positive NSCLC in this retrospective analysis. All received crizotinib 250 mg twice daily between March 2016 and April 2018 at the Fudan University Shanghai Cancer Center. All had histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangements, which were identified by fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, or next-generation sequencing. The main outcome measures were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events.ResultsThe median age of the patients was 51.0 years; 23 (65.7%) were female and 28 (80.0%) were never smokers. All were diagnosed as having adenocarcinoma; eight patients (22.9%) had brain metastases at baseline. The ORR and DCR were 71.4% and 94.3%, respectively. The estimated median PFS was 11.0 months (95% confidence interval [CI] 7.8–14.2). The estimated median OS was 41.0 months (95% CI 22.5–59.5). Elevated transaminases (54.3%), vision disorder (25.7%), elevated blood creatinine (22.9%), diarrhea (20.0%), and vomiting (20.0%) were the most commonly reported adverse effects.ConclusionCrizotinib was effective and well tolerated in Chinese patients with ROS1-positive advanced NSCLC in real-world clinical practice. The progression sites and patterns, as well as treatments after first disease progression on crizotinib were diverse. Crizotinib beyond progressive disease and local therapy after failure of crizotinib treatment were feasible and effective in clinical practice.
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36 schema:keywords Advanced Non–Small-Cell Lung Cancer
37 BackgroundApproximately 1
38 Cancer Center
39 Chinese patients
40 ConclusionCrizotinib
41 Fudan University Shanghai Cancer Center
42 MetS
43 MethodsWe
44 NSCLC
45 Non–Small-Cell Lung Cancer
46 ObjectiveOur objective
47 ROS1
48 ROS1 rearrangement
49 ROS1-Rearranged Advanced Non‒Small-Cell Lung Cancer
50 ROS1-positive NSCLC
51 ROS1-positive advanced NSCLC
52 Shanghai Cancer Center
53 University Shanghai Cancer Center
54 activity
55 adenocarcinoma
56 advanced NSCLC
57 adverse effects
58 adverse events
59 age
60 analysis
61 anaplastic lymphoma kinase
62 antitumor activity
63 baseline
64 blood creatinine
65 brain metastases
66 cancer
67 cancer (NSCLC) harbor ROS1 rearrangements
68 cell lung cancer (NSCLC) harbor ROS1 rearrangements
69 center
70 chain reaction
71 clinical practice
72 control rate
73 creatinine
74 crizotinib
75 crizotinib 250
76 crizotinib treatment
77 diarrhea
78 disease
79 disease control rate
80 disease progression
81 disorders
82 effect
83 efficacy
84 elevated blood creatinine
85 elevated transaminases
86 events
87 failure
88 first disease progression
89 fluorescence
90 harbor ROS1 rearrangements
91 hybridization
92 inhibitors
93 kinase
94 kinase inhibitors
95 local therapy
96 lung cancer
97 lung cancer (NSCLC) harbor ROS1 rearrangements
98 lymphoma kinase
99 main outcome measures
100 marked antitumor activity
101 measures
102 median age
103 median overall survival
104 median progression-free survival
105 metastasis
106 metastatic NSCLC
107 months
108 next-generation sequencing
109 objective
110 objective response rate
111 oral small-molecule tyrosine kinase inhibitor
112 outcome measures
113 overall survival
114 patients
115 patterns
116 polymerase chain reaction
117 practice
118 progression
119 progression sites
120 progression-free survival
121 progressive disease
122 rate
123 reaction
124 real-world clinical practice
125 rearrangement
126 response rate
127 retrospective analysis
128 routine clinical practice
129 safety
130 sequencing
131 sites
132 situ hybridization
133 small-molecule tyrosine kinase inhibitors
134 smokers
135 survival
136 therapy
137 transaminase
138 transcriptase polymerase chain reaction
139 treatment
140 tyrosine kinase inhibitors
141 vision disorders
142 vomiting
143 years
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