| Background:Crizotinib has a significant effect on anaplastic lymphoma kinase(ALK)positive advanced non-small cell lung cancer(NSCLC).Previous studies have shown that continued crizotinib beyond progressive disease(CBPD)after previous crizotinib resistance could provide extra clinical benefits.Though the progression-free survival(PFS)is commonly used in anti-tumor evaluation,it cannot reflect the exact benefits of sequential application of crizotinib in CBPD patients.The purpose of this study was to investigate the real efficacy of crizotinib in ALK-positive NSCLC patients in China,and to evaluate the real clinical benefits of crizotinib in CBPD patients by using a new endpoint treatment duration(TD).Methods:Clinical data of Chinese ALK-positive advanced NSCLC patients who received crizotinib from August 2007 to November 2017 were retrospectively collected,and the objective response rate(ORR),disease control rate(DCR),PFS,TD and overall survival(OS)of patients receiving crizotinib were analyzed.Results:A total of 201 patients were enrolled in the study and 150 cases developed drug resistance after prvious crizotinib treatment at the cutoff time of this study.In the whole population,the ORR and DCR were 64.2%and 91.5%.The median PFS was 13.2(95%CI:10.8-15.6)months,and the median TD was 20.7(95%CI:15.1-26.3)months,and median OS was 50.5(95%CI:37.0-64.0)months.The median PFS of first-line and above-line treatment with crizotinib were 14.6(95%CI:11.5-17.7)months and 11.2(95%CI:8.4-14.0)months,respectively(P=0.811).The median OS of first-line and above-line treatment with crizotinib was 62.0(95%CI:37.2-86.8)months and 46.8(95%CI:35.1-58.5)months,respectively(P=0.993).The median PFS of 58 CBPD patients with sequential crizotinib therapy was 10.5(range 1.9-39.3)months.The median TD of crizotinib in CBPD and non-CBPD patients was 39.7 months and 15.0 months,respectively(P<0.001)and the median OS was 61.0 months and 41.4 months,respectively(P=0.086).In CBPD patients,the correlation between TD and OS(R=0.79)was better than that between PFS and OS(R=0.64).Conclusions:Crizotinib showed good efficacy in patients with ALK-positive advanced NSCLC.Instead of PFS,treatment duration might be a more reasonable and surrogate endpoint to evaluate the real clinical benefits in patients who received crizotinib in sequential therapy.Background:Exon 20 insertion(ex20ins)of the epidermal growth factor receptor(EGFR)gene is a rare and de novo resistant mutation in non-small cell lung cancer(NSCLC).Current studies had shown the clinically approved EGFR tyrosine kinase inhibitors(TKIs)had poor efficacy for this mutation.To date,there is a lack of report on efficacy with chemotherapeutic agents or anti-angiogenic drugs in the world,and also clinical treatment outcome among Chinese NSCLC patients is rather deficient.The purpose of this study was to investigate the real efficacy of treatment regimens including chemotherapy,currently approved EGFR-TKIs and bevacizumab in Chinese advanced NSCLC patients with EGFR ex20ins,and finally to seek an effective treatment strategy for these particular patients.Methods:Between March 17,2018 and December 20,2018,clinical and pathological data of Chinese EGFR ex20ins patients with advanced NSCLC were retrospectively collected through medical records from each institution or medical questionnaires on the internet.The objective response rate(ORR),disease control rate(DCR)and progression-free survival(PFS)is analyzed.Results:165 patients with EGFR ex20ins from 26 regions in China were included in the study.A total of 39 insertion variants were detected and reported.V769_D770insASV(38/165,23.0%)and D770_N771insSVD(29/165,17.6%)were the most common variants.Brain metastases were present at initial diagnosis in 23.0%(38/165)of patients.The ORR of first-line platinum-based chemotherapy and first-line EGFR-TKIs were 19.2%and 8.7%,respectively.The DCR was 41.3%and 8.7%,respectively.The ORR of second-line chemotherapy and second-line EGFR-TKIs were 17.1%and 5.9%,respectively,and the DCR was 60.0%and 11.8%,respectively.The median PFS of first-line platinum-based chemotherapy was significantly higher than that of first-line EGFR-TKIs(6.4 months,95%CI:5.7-7.1;vs.2.9 months,95%CI:1.5-4.3;P<0.001)and that of first-generation EGFR-TKI(6.4 months,95%CI:5.7-7.1;vs.2.0 months,95%CI:0.2-3.8;P<0.001).The median PFS of second-line chemotherapy was higher than that of second-line EGFR-TKIs(4.0 months,95%CI:3.2-4.8;vs.2.0 months,95%CI:1.1-2.9;P=0.342).The median PFS of bevacizumab combined with chemotherapy was higher than that of chemotherapy alone[first-line treatment:7.5 months(95%CI:5.6-9.4)vs.5.6 months(95%CI:2.8-8.4),P=0.221;second-line treatment:6.0 months(95%CI:4.0-8.0)vs.2.4 months(95%CI:1.8-3.0),P=0.013].Conclusions:Conventional chemotherapy as the first-line or second-line treatment for Chinese EGFR ex20ins NSCLC patients had a better efficacy than all clinically approved EGFR-TKIs.For EGFR ex20ins patients,it urgently calls for novel targeted TKIs with better efficacy and capability through the blood-brain barrier.Background:As a novelly oral tyrosine kinase inhibitor(TKI)that selectively inhibits the vascular endothelial growth factor receptor-2,apatinib has shown significant efficacy against non-small cell lung cancer(NSCLC)in studies in vitro and in vivo.However,there is no prospective data of apatinib combined with intravenous chemotherapy in China or in the world.This single-center,prospective phase ? clinical study aims to investigate the efficacy and safety of apatinib combined with pemetrexed and platinum chemotherapy as an initial or salvage regimen for patients with advanced non-squamous NSCLC.Methods:Non-squamous NSCLC patients with locally advanced or metastatic disease were enrolled and received oral apatinib(250mg once daily)combined with intravenous pemetrexed(500mg/m2,day 1)and platinum(carboplatin AUC=5 or cisplatin 75mg/m2,day 1)chemotherapy for each treatment cycle of every 21 days.Efficacy was assessed every 2 treatment cycles.After 6 treatment cycles,patients were administered apatinib(250mg once daily)as maintainance until the progressive disease or unacceptable adverse events.Objective response rate(ORR)was the major endpoint in the study,while the secondary endpoints included progression-free survival(PFS),disease control rate(DCR),and drug safety.Results:A total of 20 patients with lung adenocarcinoma were enrolled in this study.Half developed progressive disease after previous TKI treatment and the other part were treatment naive.The median treatment cycle was 6(range 4-6).Partial response in 16 patients(80.0%)and stable disease in 4 patients(20.0%)as best response were observed in the study.The ORR was 16/20(80%)and the DCR was 20/20(100%).The median PFS of total patients was 7.7(95%CI:3.1-12.3)months.The ORR in TKI-pretreated group and treatment-naive group were 9/10 and 7/10,respectively,and the median PFS was 8.9(95%CI:5.5-12.3)and 5.7(95%CI:0.1-11.3)months,respectively(P=0.433).At the cutoff time,median overall survival was not reached.The 12-month survival rate was 75%(15/20).Treatment-related adverse events were mainly grade ? to ?,including hand-foot syndrome,hypertension,diarrhea,proteinuria,mucosal reactions,bone marrow suppression,or gastrointestinal distress.Grade ? to ? adverse events were only leukopenia and neutropenia associated with chemotherapy drugs.Conclusions:Apatinib combined with pemetrexed and platinum chemotherapy showed good efficacy and safety in chemo-naive patients with advanced non-squamous NSCLC in China. |
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