Background:The initial phase II stuty(NCT03215693)demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory,anaplastic lymphoma kinase(ALK)-positive non-small cell lung c...Background:The initial phase II stuty(NCT03215693)demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory,anaplastic lymphoma kinase(ALK)-positive non-small cell lung cancer(NSCLC).Herein,we reported the updated data on overall survival(OS)and molecular profiling from the initial phase Ⅱ study.Methods:In this study,180 patients received 225 mg of ensartinib orally once daily until disease progression,death or withdrawal.OS was estimated by Kaplan‒Meier methods with two-sided 95%confidence intervals(CIs).Next-generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib.Circulating tumor DNA(ctDNA)was detected to dynamically monitor the genomic alterna-tions during treatment and indicate the existence of molecular residual disease,facilitating improvement of clinical management.Results:At the data cut-off date(August 31,2022),with a median follow-up time of 53.2 months,97 of 180(53.9%)patients had died.The median OS was 42.8 months(95%CI:29.3-53.2 months).A total of 333 plasma samples from 168 patients were included for ctDNA analysis.An inferior OS correlated sig-nificantly with baseline ALK or tumor protein 53(TP53)mutation.In addition,patients with concurrent TP53 mutations had shorter OS than those without con-current TP53 mutations.High ctDNA levels evaluated by variant allele frequency(VAF)and haploid genome equivalents per milliliter of plasma(hGE/mL)at baseline were associated with poor OS.Additionally,patients with ctDNA clear-ance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth,respectively.Furthermore,patients who had a lower tumor burden,as evaluated by the diameter of target lesions,had a longer OS.Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases,higher hGE,and elevated ALK mutation abundance at 6 weeks.Conclusion:Ensartinib led to a favorable OS in patients with advanced,crizotinib-resistant,and ALK-positive NSCLC.Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.展开更多
文摘Background:The initial phase II stuty(NCT03215693)demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory,anaplastic lymphoma kinase(ALK)-positive non-small cell lung cancer(NSCLC).Herein,we reported the updated data on overall survival(OS)and molecular profiling from the initial phase Ⅱ study.Methods:In this study,180 patients received 225 mg of ensartinib orally once daily until disease progression,death or withdrawal.OS was estimated by Kaplan‒Meier methods with two-sided 95%confidence intervals(CIs).Next-generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib.Circulating tumor DNA(ctDNA)was detected to dynamically monitor the genomic alterna-tions during treatment and indicate the existence of molecular residual disease,facilitating improvement of clinical management.Results:At the data cut-off date(August 31,2022),with a median follow-up time of 53.2 months,97 of 180(53.9%)patients had died.The median OS was 42.8 months(95%CI:29.3-53.2 months).A total of 333 plasma samples from 168 patients were included for ctDNA analysis.An inferior OS correlated sig-nificantly with baseline ALK or tumor protein 53(TP53)mutation.In addition,patients with concurrent TP53 mutations had shorter OS than those without con-current TP53 mutations.High ctDNA levels evaluated by variant allele frequency(VAF)and haploid genome equivalents per milliliter of plasma(hGE/mL)at baseline were associated with poor OS.Additionally,patients with ctDNA clear-ance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth,respectively.Furthermore,patients who had a lower tumor burden,as evaluated by the diameter of target lesions,had a longer OS.Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases,higher hGE,and elevated ALK mutation abundance at 6 weeks.Conclusion:Ensartinib led to a favorable OS in patients with advanced,crizotinib-resistant,and ALK-positive NSCLC.Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.
