MOESM1 of A multicenter, retrospective epidemiologic survey of the clinical features and management of bone metastatic disease in China

Additional file 1. Questionnaire for survey of the clinical features and management of bone metastatic disease in China

Direct comparison of TKI versus chemotherapy in EGFR exon 21 L858R mutations cohort in terms of HR for PFS. CI = confidence interval; EGFR = epidermal growth factor receptor; HR = Hazard ratio; PFS = progression-free survival; TKI = tyrosine kinase inhibitor.

<p>Direct comparison of TKI versus chemotherapy in EGFR exon 21 L858R mutations cohort in terms of HR for PFS. CI  =  confidence interval; EGFR  =  epidermal growth factor receptor; HR  =  Hazard ratio; PFS  =  progression-free survival; TKI  =  tyrosine kinase inhibitor.</p

Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

<div><p>Backgrounds</p><p>It has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered.</p><p>Methods</p><p>Subgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively.</p><p>Results</p><p>A total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20–0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35–0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation  = 0.59, 95% CI 0.38–0.92; P = 0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation  = 0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies.</p><p>Conclusions</p><p>For advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs.</p></div

Profile summarizing the trial flow.

<p>CI  =  confidence interval; EGFR  =  epidermal growth factor receptor; HR  =  Hazard ratio; PFS  =  progression-free survival; TKI  =  tyrosine kinase inhibitor.</p

Indirect comparison of EGFR exon 19 deletion versus EGFR exon 21 L858R mutation in TKI therapy cohort in terms of HR for PFS.

a<p>HR_19/21 of TKI represents HR_{19 exon deletion/exon 21 L858R mutation} in TKI therapy cohort.</p><p>Abbreviations: CI  =  confidence interval; EGFR  =  epidermal growth factor receptor; HR  =  Hazard ratio; PFS  =  progression-free survival; TKI  =  tyrosine kinase inhibitor.</p><p>Indirect comparison of EGFR exon 19 deletion versus EGFR exon 21 L858R mutation in TKI therapy cohort in terms of HR for PFS.</p

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Geometric distribution of indirect comparisons.

<p>Solid lines between regimens represented the existence of direct comparisons. Chemo  =  chemotherapy; EGFR  =  epidermal growth factor receptor; TKI  =  tyrosine kinase inhibitor.</p

The Efficacy of Combining Antiangiogenic Agents with Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer Who Failed First-Line Chemotherapy: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>The clinical outcomes of patients with NSCLC who progressed after first-line treatments remain poor. The purpose of this study was to assess the advantage of antiangiogenic therapy plus standard treatment versus standard treatment alone for this population of patients.</p><p>Methods</p><p>We conducted a rigorous search using electronic databases for eligible studies reporting antiangiogenic therapy combined with standard second-line chemotherapy versus standard second-line treatment for patient who progressed after front-line treatment. Pooled risk ratio and 95% confidence intervals were calculated using proper statistical method. Predefined subgroup analyses were conducted to identify the potential proper patients.</p><p>Results</p><p>Thirteen phase II/III RCTs which involved a total of 8358 participants were included. Overall, there was significant improvement in OS (HR 0.94, 95%CI: 0.89-0.99, p=0.03), PFS (HR 0.80, 95%CI: 0.76-0.84, p<0.00001), ORR (RR 1.75, 95%CI: 1.55-1.98, p<0.00001) and DCR (RR 1.23, 95%CI: 1.18-1.28, p<0.00001) in the group with antiangiogenic therapy plus standard treatment versus the group with standard treatment alone. Subgroup analysis showed that OS benefit was presented only in patients treated with docetaxel plus antiangiogenic agents (HR 0.92, 95%CI: 0.86-0.99, p=0.02) and patients with non-squamous NSCLC (HR for OS 0.92, 95%CI: 0.86-0.99, p=0.02).</p><p>Conclusions</p><p>This study revealed that the addition of antiangiogenic agents to the standard treatments could provide clinical benefit to NSCLC patients who failed their first-line therapy. Furthermore, proper selection of the combined standard cytotoxic agent, as well as the patient population by tumor histology, is warranted for future studies and clinical application of antiangiogenic therapy.</p></div

The optimal cut-off point plots generated by the biostatistical tool, <i>Cut-off Finder</i>.

<p>The vertical line designates the optimal cut-off point with the most significant <i>(log-rank test)</i> split.</p

Forest plot for subgroup analysis of overall survival.

<p>Survival is for high PNI vs low PNI. Data are derived from Cox’s analysis without covariates.</p