肺癌靶向治疗进展－2012（周彩存）

肺癌靶向治疗进展－2012 同济大学附属上海市肺科医院肿瘤科 周彩存 Targeting the Epidermal Growth Factor Receptor EGFR突变： EGFR TKI一线首选 西妥昔单抗在晚期NSCLC治疗中地 位？ SELECT 第二代EGFR TKI有效 LUX-Lung 3 PF-299 [TITLE] Supplementary analysis: influence of EGFR TKI and chemotherapy on OS Patients at risk Patients receiving chemo only* 21 17 12 8 6 4 3 0 Patients receiving EGFR TKI only‡ 33 32 27 24 17 12 7 0 Patients receiving EGFR TKI and chemo§ 94 94 89 80 68 60 28 6 1.0 0.8 0.6 0.4 0.2 0 0 5 10 15 20 25 30 35 40 Time (months) O S p r o b a b i l i t y Patients receiving EGFR TKI and chemo vs patients receiving chemo only p=0.0001 Patients receiving EGFR TKI only vs patients receiving chemo only p=0.057 Log-rank p value <0.0001 n Events n (%) Median (months) 95% CI Received chemo only* 21 17 (81) 11.70 7.29–22.87 Received EGFR TKI only‡ 33 22 (67) 20.67 16.62–28.32 Received EGFR TKI and chemo§ 94 50 (53) 30.39 25.99–NR *Chemo only, no EGFR TKI: patients from the GC arm who had no further treatment (n=16) or further chemotherapy (n=5) ‡EGFR TKI only, no chemo: patients from the erlotinib arm who are still on treatment (n=7), had no further treatment (n=25) and who were re-challenged (n=1) §EGFR TKI and chemo: patients from the erlotinib arm who switched to chemo (n=43), patients from the GC arm who switched to erlotinib in any line (n=51) [TITLE] Primary endpoint: PFS Independent review ‒ all randomized patients P r o g r e s s i o n - f r e e s u r v i v a l ( p r o b a b i l i t y ) 1.0 0.8 0.6 0.4 0.2 0.0 Number at risk Afatinib 230 180 151 120 77 50 31 10 3 0 Cis/Pem 115 72 41 21 11 7 3 2 0 0 Progression-free survival (months) 0 3 6 9 12 15 18 21 24 27 Afatinib n=230 Cis/pem n=115 PFS event, n (%) 152 (66) 69 (60) Median PFS (months) 11.1 6.9 Hazard ratio (95% confidence interval) 0.58 (0.43–0.78) P=0.0004 47% 22% Yang JC, et al. P r o g r e s s i o n - f r e e s u r v i v a l ( p r o b a b i l i t y ) 1.0 0.8 0.6 0.4 0.2 0.0 Number at risk Afatinib 204 169 143 115 75 49 30 10 3 0 Cis/Pem 104 62 35 17 9 6 2 2 0 0 Progression-free survival (months) 0 3 6 9 12 15 18 21 24 27 Afatinib n=204 Cis/pem n=104 PFS event, n (%) 130 (64) 61 (59) Median PFS (months) 13.6 6.9 Hazard ratio (95% confidence interval) 0.47 (0.34–0.65) P<0.0001 PFS: Common mutations (Del19/L858R) Independent review – patients with Del 19/L858R (n=308) Yang JC, et al. [TITLE] [TITLE] First-line dacomitinib (PF-00299804), an irreversible pan-HER tyrosine kinase inhibitor for patients with EGFR-mutant lung cancer MG Kris, Mok , SHI Ou, et al. [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] Benjamin Besse. ASCO 2012 [TITLE] Conclusions 第一代，二代EGFR TKI治疗EGFR突变晚期NSCLC有效 较好的PFS，缓解率，生存质量与安全性 OS无差异 第二代EGFR TKI有少见EGFR突变似乎有效 第二代TKI不良反应>第一代TKI 西妥昔单抗联合二线化疗：无效 第二代耐药机制： T790M，c-MET扩增？ 结论  NSCLC是由不同驱动基因突变的NSCLC所组 成  MEK抑制剂联合化疗对KRAS突变NSCLC可 能有效  ALK耐药机制多种多样，并且可以druggable  抗血管生成的小分子抑制剂联合化疗在晚期 NSCLC未见疗效 肺癌靶向治疗进展－2012 幻灯片编号 2 幻灯片编号 3 幻灯片编号 4 [TITLE] Supplementary analysis: influence of EGFR TKI and chemotherapy on OS [TITLE] Primary endpoint: PFS �Independent review ‒ all randomized patients PFS: Common mutations (Del19/L858R)�Independent review – patients with Del 19/L858R (n=308) [TITLE] [TITLE] 幻灯片编号 12 [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] [TITLE] 结论