Objective: to systematically evaluate and compare the efficacy and safety of 14 treatment options in patients with EGFR 19DEL mutation and EGFR 21L858R mutation in non-small cell lung cancer. Methods: the Pubmed, Coch...Objective: to systematically evaluate and compare the efficacy and safety of 14 treatment options in patients with EGFR 19DEL mutation and EGFR 21L858R mutation in non-small cell lung cancer. Methods: the Pubmed, Cochrane, Embase database and ASCO, ESMO, and WCLC conferences were retrieved to collect clinical randomized controlled trials (RCT) of first-line EGFR-related non-small cell lung cancer with TKIs. Based on the grouping of EGFR mutation types, Bayesian mesh meta-analysis (NMA) was performed by using GEMTC package Markov chain Monte Carlosimulation with R software, comparing the difference between progression-free survival (PFS) and grade 3 or above adverse reactions (≥3AES) in EGFR 19DEL and EGFR 21L858R mutations in patients with each treatment regimen. In addition, the efficacy and safety of the 14 treatment options were ranked according to the cumulative area of SUCRA (EGFR mutation type).Results: a total of 22 RCTs were included in the study, involving 14 treatment regimens. NMA results showed that for patients with EGFR 19DEL mutation, all EGFR TKIs related treatment schemes could prolong PFS more than chemotherapy, especially AUM and OSI (AUM vs PB:HR 0.17, 95%CI 0.08 ~ 0.35;OSI vs PB:HR 0.18, 95%CI 0.08 ~ 0.38);For patients with EGFR 21L858R mutation, GEF+PB and OSI could prolong PFS most (GEF+PB vs PB:HR 0.30, 95%CI 0.14 ~ 0.56;OSI vs PB:HR 0.35, 95%CI 0.15 ~ 0.74). Sucra ranking results showed that for patients with EGFR 19DEL mutation, AUM, OSI, GEF+PB ranked first, second and third in PFS respectively, while for patients with EGFR 21L858R mutation, the top three schemes were GEF+PB, OSI and ERL+BEV respectively. Conclusion: AUM and GEF+PB are the best treatment options for patients with EGFR 19DEL mutation and EGFR 21L858R mutation, respectively.展开更多
Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line se...Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line second generation EGFR tyrosine kinase inhibitors （TKIs） afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups. Methods： Eligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios （HRs）. All measures were pooled using random- effects models and 95% confidential interval （95% CI） was calculated. Results： A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials （RCTs）, first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy （pooled HR_TKI/Chemo for Del19： 0.82, 95% CI： 0.64- 1.06, P=0.14; pooled HR_TKI/Chemo for L858R： 1.15, 95% CI： 0.85-1.56, P=0.38）. Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference （pooled HR19/21： 0.88, 95% CI： 0.67-1.16, P=0.37）. Conclusions： Among patients with advanced non-small cell hmg cancer （NSCLC） harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.展开更多
文摘Objective: to systematically evaluate and compare the efficacy and safety of 14 treatment options in patients with EGFR 19DEL mutation and EGFR 21L858R mutation in non-small cell lung cancer. Methods: the Pubmed, Cochrane, Embase database and ASCO, ESMO, and WCLC conferences were retrieved to collect clinical randomized controlled trials (RCT) of first-line EGFR-related non-small cell lung cancer with TKIs. Based on the grouping of EGFR mutation types, Bayesian mesh meta-analysis (NMA) was performed by using GEMTC package Markov chain Monte Carlosimulation with R software, comparing the difference between progression-free survival (PFS) and grade 3 or above adverse reactions (≥3AES) in EGFR 19DEL and EGFR 21L858R mutations in patients with each treatment regimen. In addition, the efficacy and safety of the 14 treatment options were ranked according to the cumulative area of SUCRA (EGFR mutation type).Results: a total of 22 RCTs were included in the study, involving 14 treatment regimens. NMA results showed that for patients with EGFR 19DEL mutation, all EGFR TKIs related treatment schemes could prolong PFS more than chemotherapy, especially AUM and OSI (AUM vs PB:HR 0.17, 95%CI 0.08 ~ 0.35;OSI vs PB:HR 0.18, 95%CI 0.08 ~ 0.38);For patients with EGFR 21L858R mutation, GEF+PB and OSI could prolong PFS most (GEF+PB vs PB:HR 0.30, 95%CI 0.14 ~ 0.56;OSI vs PB:HR 0.35, 95%CI 0.15 ~ 0.74). Sucra ranking results showed that for patients with EGFR 19DEL mutation, AUM, OSI, GEF+PB ranked first, second and third in PFS respectively, while for patients with EGFR 21L858R mutation, the top three schemes were GEF+PB, OSI and ERL+BEV respectively. Conclusion: AUM and GEF+PB are the best treatment options for patients with EGFR 19DEL mutation and EGFR 21L858R mutation, respectively.
文摘Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line second generation EGFR tyrosine kinase inhibitors （TKIs） afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups. Methods： Eligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios （HRs）. All measures were pooled using random- effects models and 95% confidential interval （95% CI） was calculated. Results： A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials （RCTs）, first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy （pooled HR_TKI/Chemo for Del19： 0.82, 95% CI： 0.64- 1.06, P=0.14; pooled HR_TKI/Chemo for L858R： 1.15, 95% CI： 0.85-1.56, P=0.38）. Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference （pooled HR19/21： 0.88, 95% CI： 0.67-1.16, P=0.37）. Conclusions： Among patients with advanced non-small cell hmg cancer （NSCLC） harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.
