Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the...Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the survival difference between exon 19 deletion （Dell9） and exon 21 Leu858Arg substitution （L858R） remains controversial. The purpose of this study is to investigate the differences in progression-free survival （PFS） and overall survival （OS） between different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib. Methods： There were 204 advanced NSCLC patients with EGFR mutations treated with gefitinib were enrolled in this retrospective cohort study. Patients were divided into the EGFR Dell9 group and the L858R mutated group according to their mutant subtype. Propensity score matching （PSM） was conducted by using a nearest-neighbor algorithm （1：1） to adjust for demographical and clinical covariates. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results： The PFS in Dell9 group was similar to that in the L858R group [before PSM 8.6 vs. 7.2 months, P=0.072; after PSM 7.3 vs. 7.2 months, P=0.155]. No differences were detected in OS between the L858R and the Dell9 group （before PSM 17.8 vs. 13.1 months, P=0.253; after PSM 16.9 vs. 13.1 months, P=0.339）. The Dell9 group was significantly younger compared with the L858R mutation group in age （P=0.015）. Conclusions： No significant difference was found in the PFS or OS between the Dell9 and L858R mutant NSCLC patients receiving gefitinib. The age gap might contribute to the survival differences between Dell9 and L858R groups. PSM is of important value to the elimination of potential bias.展开更多
Objective: Biological markers performable in routine practice and able to predict the clinical outcome of advanced non-small cell lung cancer (NSCLC) treated with gefitinib are urgently needed. Methods: We analyzed EG...Objective: Biological markers performable in routine practice and able to predict the clinical outcome of advanced non-small cell lung cancer (NSCLC) treated with gefitinib are urgently needed. Methods: We analyzed EGFR / HER2 / HER3 primary tumour immunohistochemical expression in a prospective and consecutive series of 90 Chinese patients. Platinum- pretreated patients received a 250 mg oral dose of gefitinib once daily until disease progression; EGFR / HER2 / HER3 tumour status was related with the clinical outcome in terms of response rate (RR), time to disease progression (TTP), and overall survival (OS). Results: A high expression (scores 2-3) of EGFR, HER2 and HER3 was verified in 16.7%, 43.3% and 21.1% of tumors, respectively. EGFR and HER3 status were not significantly related with response, while the HER2 overexpression result was significantly associated with a higher RR (35.9% vs. 15.7%, P = 0.027). The RR in the 13 patients with both HER2 and HER3 expression was also significantly higher than in the other 77 patients (53.8% vs. 22.1%, P = 0.036). EGFR / HER2 / HER3 status was not significantly correlated with TTP or OS. Conclusion: The HER2 immunohistochemical expression can play a role in the clinical management of Chinese patients with advanced NSCLC who are candidates for gefitinib therapy.展开更多
Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin...Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting.展开更多
基金supported by the Beijing Natural Science Foundation(Commission No.7162038)the Beijing Municipal Administration of Hospitals’Youth Program(Commission No.QML20161101)
文摘Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the survival difference between exon 19 deletion （Dell9） and exon 21 Leu858Arg substitution （L858R） remains controversial. The purpose of this study is to investigate the differences in progression-free survival （PFS） and overall survival （OS） between different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib. Methods： There were 204 advanced NSCLC patients with EGFR mutations treated with gefitinib were enrolled in this retrospective cohort study. Patients were divided into the EGFR Dell9 group and the L858R mutated group according to their mutant subtype. Propensity score matching （PSM） was conducted by using a nearest-neighbor algorithm （1：1） to adjust for demographical and clinical covariates. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results： The PFS in Dell9 group was similar to that in the L858R group [before PSM 8.6 vs. 7.2 months, P=0.072; after PSM 7.3 vs. 7.2 months, P=0.155]. No differences were detected in OS between the L858R and the Dell9 group （before PSM 17.8 vs. 13.1 months, P=0.253; after PSM 16.9 vs. 13.1 months, P=0.339）. The Dell9 group was significantly younger compared with the L858R mutation group in age （P=0.015）. Conclusions： No significant difference was found in the PFS or OS between the Dell9 and L858R mutant NSCLC patients receiving gefitinib. The age gap might contribute to the survival differences between Dell9 and L858R groups. PSM is of important value to the elimination of potential bias.
文摘Objective: Biological markers performable in routine practice and able to predict the clinical outcome of advanced non-small cell lung cancer (NSCLC) treated with gefitinib are urgently needed. Methods: We analyzed EGFR / HER2 / HER3 primary tumour immunohistochemical expression in a prospective and consecutive series of 90 Chinese patients. Platinum- pretreated patients received a 250 mg oral dose of gefitinib once daily until disease progression; EGFR / HER2 / HER3 tumour status was related with the clinical outcome in terms of response rate (RR), time to disease progression (TTP), and overall survival (OS). Results: A high expression (scores 2-3) of EGFR, HER2 and HER3 was verified in 16.7%, 43.3% and 21.1% of tumors, respectively. EGFR and HER3 status were not significantly related with response, while the HER2 overexpression result was significantly associated with a higher RR (35.9% vs. 15.7%, P = 0.027). The RR in the 13 patients with both HER2 and HER3 expression was also significantly higher than in the other 77 patients (53.8% vs. 22.1%, P = 0.036). EGFR / HER2 / HER3 status was not significantly correlated with TTP or OS. Conclusion: The HER2 immunohistochemical expression can play a role in the clinical management of Chinese patients with advanced NSCLC who are candidates for gefitinib therapy.
基金China National Major Project for New Drug Innovation,Grant/Award Number:2017ZX09304015Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS),Grant/Award Number:2016-I2M-1-001。
文摘Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting.
