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The Efficacy and Safety of Ceritinib in the Treatment of ALK+ NSCLC: A Systematic Review and Meta-Analysis
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A7339 - The Efficacy and Safety of Ceritinib in the Treatment of ALK+ NSCLC: A Systematic Review and Meta-Analysis
Author Block: P. Luo1, J. Fan2, Z. Xia1, X. Zhang1, Y. Chen1, R. Qian1, S. Liu1, D. You1, J. Zhang1; 1Southern Medical University, Guangzhou, China, 2Shanghai Tenth People’s Hospital, Tongji University,, Shanghai, China.
Background: Ceritinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor approved by the Food and Drug Administration (FDA) to treat crizotinib-refractory non-small cell lung cancer (NSCLC). The current meta-analysis attempted to pool the results of different clinical trials to evaluate the efficacy and safety of ceritinib. Method: A search of three databases including PubMed, Web of Science and the Cochrane Library was performed from the inception of each database through October 15, 2017. We have pooled the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), 12 months overall survival (OS) rate, and intracranial ORR, intracranial DCR to evaluate the efficacy of ceritinib. Discontinuation rate due to adverse events (AEs), rate of dose reduction or interruption, the event rate of AEs of all grade and grade 3-4, as well as severe adverse events (SAEs) which were suspected to be treatment-related along with the incidence of several AEs were aggregated to evaluate its safety. Result: A total of 9 studies with 1541 patients have been included in our study. The pooled efficacy parameters are as follows: ORR 56% (95%CI 46-65%), DCR 81% (95%CI 75-86%), PFS 7.74 months (95%CI 6.02-9.46), 12-month OS 77% (95%CI 68-85%) and intracranial ORR 39% (95%CI 26-51%), intracranial DCR 80% (95%CI 72-88%). ALKi-naïve patients tend to have better responses than crizotinib-pretreated patients. The aggregate AE caused discontinuation rate is 8% (95%CI 7-10%). Pooled rate of dose reduction and interruption were 59% (95%CI 55-63%) and 76% (95%CI 72-79%) respectively. Pooled results showed that approximately 92% (95%CI 87-96%) patients would experience drug-related AEs and 48% (95%CI 37-60%) patients would experience grade 3-4 AEs. About 11% (95%CI 7-16%) patients would suffer from SAEs suspected to be caused by ceritinib treatment. Most frequently reported AEs were diarrhea (80%, (95%CI 75-85%)), nausea (72%, (95%CI 65-79%)) and vomiting (61%, (95%CI 55-66%)). Most frequently reported grade 3-4 AEs were increased ALT (20%, (95%CI 11-29%)), increased GGT (15%, (95%CI 5-26%)) and increased AST (9%, (95%CI 4-14%)). Conclusion: Generally, ceritinib is a drug with preferable efficacy. However, its safety is far from satisfactory. Ceritinib may be a suitable second- or third- line treatment for crizotinib or alectinib resistant patients rather than being prescribed as a first-line treatment.
Author Block: P. Luo1, J. Fan2, Z. Xia1, X. Zhang1, Y. Chen1, R. Qian1, S. Liu1, D. You1, J. Zhang1; 1Southern Medical University, Guangzhou, China, 2Shanghai Tenth People’s Hospital, Tongji University,, Shanghai, China.
Background: Ceritinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor approved by the Food and Drug Administration (FDA) to treat crizotinib-refractory non-small cell lung cancer (NSCLC). The current meta-analysis attempted to pool the results of different clinical trials to evaluate the efficacy and safety of ceritinib. Method: A search of three databases including PubMed, Web of Science and the Cochrane Library was performed from the inception of each database through October 15, 2017. We have pooled the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), 12 months overall survival (OS) rate, and intracranial ORR, intracranial DCR to evaluate the efficacy of ceritinib. Discontinuation rate due to adverse events (AEs), rate of dose reduction or interruption, the event rate of AEs of all grade and grade 3-4, as well as severe adverse events (SAEs) which were suspected to be treatment-related along with the incidence of several AEs were aggregated to evaluate its safety. Result: A total of 9 studies with 1541 patients have been included in our study. The pooled efficacy parameters are as follows: ORR 56% (95%CI 46-65%), DCR 81% (95%CI 75-86%), PFS 7.74 months (95%CI 6.02-9.46), 12-month OS 77% (95%CI 68-85%) and intracranial ORR 39% (95%CI 26-51%), intracranial DCR 80% (95%CI 72-88%). ALKi-naïve patients tend to have better responses than crizotinib-pretreated patients. The aggregate AE caused discontinuation rate is 8% (95%CI 7-10%). Pooled rate of dose reduction and interruption were 59% (95%CI 55-63%) and 76% (95%CI 72-79%) respectively. Pooled results showed that approximately 92% (95%CI 87-96%) patients would experience drug-related AEs and 48% (95%CI 37-60%) patients would experience grade 3-4 AEs. About 11% (95%CI 7-16%) patients would suffer from SAEs suspected to be caused by ceritinib treatment. Most frequently reported AEs were diarrhea (80%, (95%CI 75-85%)), nausea (72%, (95%CI 65-79%)) and vomiting (61%, (95%CI 55-66%)). Most frequently reported grade 3-4 AEs were increased ALT (20%, (95%CI 11-29%)), increased GGT (15%, (95%CI 5-26%)) and increased AST (9%, (95%CI 4-14%)). Conclusion: Generally, ceritinib is a drug with preferable efficacy. However, its safety is far from satisfactory. Ceritinib may be a suitable second- or third- line treatment for crizotinib or alectinib resistant patients rather than being prescribed as a first-line treatment.
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