2014 ASCO克唑替尼及ALK阳性NSCLC最新进展-1PPT.pptx

2014 ASCO——克唑替尼及ALK阳性NSCLC最新进展克唑替尼在ALK 阳性的晚期非鳞非小细胞肺癌一线治疗中与化疗对比PROFILE 1014Mok T, Kim D-W, Wu Y-L, et al. First-line crizotinib versus pemetrexed?cisplatin or pemetrexed?carboplatin in patients with advanced ALK-positive non-squamous non-small cell lung cancer: Results of a phase III study (PROFILE 1014). Poster presented at the 50th Annual ASCO Meeting, Chicago, IL, USA, May 30 ? June 3, 2014 (Abstract 8002)研究设计 January 2011 to July 2013研究终点主要终点PFS (RECIST v1.1,独立放射学评审)次要终点ORROS安全性 患者生活质量报告(EORTC QLQ-C30, LC13)主要入选标准FISH法测定ALK阳性a局部晚期，复发或转移非鳞NSCLC 无既往治疗的晚期患者ECOG PS 0?2病灶可测量经治稳定的脑转移患者可入组克唑替尼 250 mg BID PO, 连续用药(N=172)随机分组培美曲塞 500 mg/m2 + 顺铂 75 mg/m2 或卡铂 AUC 5–6 q3周方案治疗 ≤6 个周期(N=171)bN=343疾病进展后交叉至克唑替尼组c a FISH法测定ALK状态b分层因素: ECOG PS (0/1 vs. 2), 亚洲人 vs. 非亚洲人, 脑转移 c独立放射学评审评估PROFILE 1014: NC床基线特征(全体分析人群)特征克唑替尼 (N=172)化疗 (N=171)年龄, 岁中位(范围)52 (22–76)54 (19–78)性别, n (%)男68 (40)63 (37)种族, n (%)高加索人亚洲人其他91 (53)77 (45)4 (2)85 (50)80 (47)6 (4)吸烟, n (%)无吸烟史既往吸烟目前吸烟106 (62)56 (33)10 (6)112 (65)54 (32)5 (3)组织学, n (%)腺癌大细胞癌腺鳞癌其他158 (92)3 (2)5 (3)6 (3)159 (93)8 (5)1 (1)3 (2)ECOG PS,a n (%)0/12161 (94)10 (6)163 (95)8 (5)距离首次诊断的时间, 月中位 (范围）1.2 (0.0–114.0)1.2 (0.0–93.6)脑转移, n (%)存在45 (26)47 (27)aAt screening; data for 1 patient missing for crizotinibMok T, et al. Poster presented at ASCO 2014 (Abstract 8002)独立影像学评估的PFS(全体分析人群) 克唑替尼(N=172)化疗(N=171)事件, n (%)100 (58)137 (80)中位, 月10.97.0风险比率 (95% CI)0.45 (0.35?0.60)Pa0.00011008060PFS probability (%)40200 0 5 10 15 20 25 30 35时间 (月)风险人数克唑替尼化疗 172 120 65 38 19 7 1 0 171 105 36 12 2 1 0 0a1-sided stratified log-rank testMok T, et al. Poster presented at ASCO 2014 (Abstract 8002)独立影像学评估的ORR??克唑替尼(N=172)化疗a(N=171)ORR, % (n)74 (128)45 (77) ORR 95% 置信区间 CI67–8137–53治疗差异, % 95% Cib29 20?39 Pb 0.0001到达缓解的中位时间,c 周?6.112.1 数值范围2.7?41.45.1?36.7缓解持续中位时间,c,d 周49.022.9 95% CIe35.1?60.018.0?25.1ORR (95% exact CI; %)克唑替尼化疗A交叉至克唑替尼组之前bPearson χ2 test C客观缓解的患者 dKaplan?Meier methodeBrookmeyer?Crowley methodMok T, et al. Poster presented at ASCO 201