非小细胞肺癌精准治疗新进展-关注脑转移课件

Antitumor Activity − PFS and ORRa
ITT population Crizotinib Chemo (N=172) (N=171) Brain metastases presentb Crizotinib Chemo (n=39) (n=40)
Brain metastases absentb Crizotinib Chemo (n=132) (n=131) 11.1 (8.3–14.0) 7.2 (6.9–8.3)
Median PFS, mo (95% CI)
HR (95% CI) Pc
10.9 (8.3–13.9)
7.0 (6.8ຫໍສະໝຸດ Baidu8.2)
9.0 (6.8–15.0)
4.0 (1.5–6.8)
0.45 (0.35–0.60) <0.001
0.40 (0.23–0.69) <0.001
0.51 (0.38–0.69) <0.001
Abstract 1238
Baseline Characteristics of Patients With/without Brain Metastases at Baselinea
Brain metastasesb present Chemo (n=40) 51 (25−76) 9 (23) 19 (48) 18 (45) 3 (8) 28 (70) 12 (30) 0 38 (95) 0 1 (3) 1 (3) 34 (85) 6 (15) 2.4 (1.2−74.4) Brain metastases absent Characteristic Age, years Sex, n (%) Race, n (%) Median (range) Male Caucasian Asian Other Never smoked Ex-smoker Current smoker Adenocarc. Large cell carc. Adenosquamous carc. Other 0/1 2 Median (range) Crizotinib (n=39) 48 (29−70) 20 (51) 20 (51) 17 (44) 2 (5) 23 (59) 13 (33) 3 (8) 35 (90) 1 (3) 2 (5) 1 (3) 35 (90) 4 (10) 2.4 (0−36.0) Crizotinib (n=132) Chemo (n=131) 53 (22−76) 47 (36) 70 (53) 60 (45) 2 (2) 83 (63) 43 (33) 6 (5) 123 (93) 2 (2) 3 (2) 4 (3) 125 (95) 6 (5) 1.2 (0−114.0) 56 (19−78) 54 (41) 66 (50) 62 (47) 3 (2) 84 (64) 42 (32) 5 (4) 121 (92) 8 (6) 0 2 (2) 129 (98) 2 (2) 1.2 (0−93.6)
N=343
Crossover to crizotinib permitted after progressiond
● Intracranial efficacy was prospectively evaluated in the ITT population and patients with and without brain metastases at baselinee
2015非小细胞肺癌个体化治疗 新进展
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内 容
•ALK+ NSCLC脑转移的治疗 •EGFR+ NSCLC脑转移的治疗
PROFILE 1014脑转移亚组分析：克唑 替尼一线治疗与化疗比较的颅内疗效分析
Key entry criteria ● ALK-positive by central FISH testinga ● Locally advanced, recurrent, or metastatic non-squamous NSCLC ● No prior systemic treatment for advanced disease ● ECOG PS 0−2 Endpoints R A N D O M I Z Ec Crizotinib 250 mg BID PO, continuous dosing (n=172) ● Primary – PFS (RECIST 1.1, independent radiologic review [IRR]) ● Secondary – ORR – OS – Intracranial TTPe – Safety – Patient-reported outcomes
ORR, % (95% exact CI) Differenced (95% exact CI) Pe
74 (67−81)
45 (37−53) 29 (20−39) <0.001
77 (61−89) 49 (30−69) <0.001
28 (15−44)
74 (66−82)
Smoking, n (%)
Histology, n (%)
ECOG PS,c n (%) Time since first diagnosis, mo
Carc., carcinoma; aby IRR; bpreviously treated per protocol, although this criterion was not fulfilled in all cases cAt screening; data for 1 patient missing for crizotinib
● Measurable disease
● Stableb treated brain metastases allowed
Pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 or carboplatin AUC 5–6 q3w for ≤6 cycles (n=171)