抗血管生成在NSCLC应用.ppt

* Differential regulation of V by egfr in different cell lines: mutated, t790m, kras -some cell lines: highly regulated V by E, some little or no regulation (a549); also different levels at baselien Point out – differentially reg by hypoxia. . . . . * * * ATLAS – progression-free survival Miller VA, et al. J Clin Oncol 2009;27(Suppl 1):Abstract LBA8002 373 142 58 27 15 6 3 0 370 178 81 43 20 6 3 1 No. of patients at risk: Bev + placebo Bev + erlotinib Progression-free survival (months) 0 3 6 9 12 15 18 21 0.0 0.2 0.4 0.6 0.8 1.0 Proportion without event HR=0.722 (0.592–0.881) Log-rank p=0.0012 Bevacizumab + placebo (n=373) Bevacizumab + erlotinib (n=370) ATLAS – update on overall survival A 40% crossover rate (placebo patients to receive E once disease progressed) and underpowered design prevented trial from reaching significance for OS analysis 2-month OS benefit was observed in the Bv and E maintenance arm after occurrence of 57% events Biomarker analysis data of ATLAS study are expected soon Kabbinavar FF,?et al. J Clin Oncol 2010;28:15s (suppl; abstr 7526) Data cut-off Patients with events, n/N (%) Median OS (months) Bv + E vs Bv HR (95% CI) 18 July 2008 (pre-specified) 228/743 (31) 14.4 vs 13.3 0.92 (0.70–1.21) 19 June 2009 439/768* (57) 15.9 vs 13.9 0.90 (0.74–1.09) *25 patients were randomized after cut-off for main analysis of PFS ECOG5508: Phase III trial of BV, Pem, or BV+Pem as maintenance therapy in advanced NSCLC Carbo/pac/BV Q3w x 4 cycles Eligibility -BV eligible -non-squam -chemonaive -no CNS mets ?PI: S. Ramilingam; ; trial NCR Non-PD BV Induction Maintenance Pem BV+Pem Primary endpoint: OS Secondary: PFS S130 trial: Phase III trial of CP+Bv?Bv vs PemCarbo+Bv?Pem in first line NSCLC Eligibility -BV eligible -non-squam -chemonaive -treated brain mets Sponsor: Lilly; from ; trial NCR Carboplatin paclitaxel+BV (15mg/kg) q3w BV Pem Carboplatin pemetrexed Induction Maintenance Primary endpoint: PF