108
0
36 时间 (月)
72
108
Venook A, et al. 2016 ASCO Abstract 3504.Leabharlann 80405：部位作为预测因素？
“肿瘤特征”指导下的的治疗策略 --- 肿瘤部位
原发肿瘤部位对于mCRC治疗的重要性？
右侧肿瘤
• • • • • 发生率： ~40% (上升) 年纪较大的患者 微卫星不稳定 更高的突变发生率 预后较差 • • • •
具有多个篮形研究设计的独特主研究方案
HER2
BRAF
Hh
EGFR
分子学改变
HER2过表达， 扩增或 活化突变
BRAF活化突变 (V600E & 其他)
SMO-活化突变， PTCH-1 功能缺失突变
EGFR 活化突变
治疗
曲妥珠单抗 +帕妥珠单抗
Vermurafenib
Vismodegib
Hainsworth J, et al. 2016 ASCO Abstract LBA11511.
Richard L. Schilsky, MD, FASCO， the first chief medical officer of ASCO
“This lab and many others are now offering these circulating tumor DNA tests. I think commercial use is getting a bit out front of the actual data that demonstrate clinical utility, but there are obvious advantages over tissue-based biopsy," he commented.
2015
MyPathway Trial
2016ASCO
“异病同治”与“同病异治”
疗效：HER2扩增/过表达肿瘤概 况(n=61)
原发部位 结直肠癌 膀胱癌 胆道癌 NSCLC 胰腺癌 头颈部肿瘤 其他(5个部位) 总计 Na 20 8 6 7 6 3 11 61 CR/PR n (%) 7 (35) 3 (38) 3 (50) 2 (29) 1 (17) 1 (33) 0 17 (28) SD>120天 n (%) 3 (15) 2 (25) 3 (50) 0 0 0 1 (9) 9 (15) 临床获益 n (%) 10 (50) 5 (63) 6 (100) 2 (29) 1 (17) 1 (33) 1 (9) 26 (43)
0 0 10 月 20 30 PFS(%) 100 中位PFS (抗EGFR) 左侧 6.5个月 (n=118) 右侧 4.7个月 (n=49) HR 1.56(1.01-2.41) P=0.040
79%
50
“In this exciting era of precision medicine, that genomics is not the only source of insight into how cancers should be studied and treated."
a包括6例扩增+突变以及1例RBMS-NRG-1融合患者 Hainsworth J, et al. 2016 ASCO Abstract LBA11511.
2015 ASCO Annual Meeting
The HERACLES trial Trastuzumab and lapatinib in HER2-amplified metastatic colorectal cancer patients (mCRC)
Dr. Mack conducts molecular biology and molecular pharmacology studies for the UC Davis Cancer Center, the California Cancer Consortium, and the Southwest Oncology Group.
精准医学时代的CRC Her-2在mCRC 液体活检 左右半——现象？方向？导向？ 免疫治疗
Abstract 3504
80405 左右差异
PFS
KRAS wt N=1025 所有患者 Cet BV 右侧 中位PFS(月) 8.9 7.8 9.6 左侧 中位PFS(月) 11.7 12.4 11.2 HR(95%CI) 1.03(1.11,1.50) 1.56(1.26,1.94) 1.06(0.86,1.31) P(校正) 0.0006 <0.0001 0.55
ASCO President Julie M. Vose, MD, MBA, FASCO,
Abstract 3505
2007年到2011年之间在SEER区域确认了原发性结直肠 癌诊断的患者，并对他们随访至2013年以确定诊断分期
FIRE-3:预后因素（右不如左）
Not exactly a new story….
Presented By Kimmie Ng at 2016 ASCO Annual Meeting
80405：OS 右不如左 与 靶向治疗
贝伐珠单抗
事件数 左侧 732(550) HR 中位 (95%CI) (95%CI) 33.3 (31.4-35.7) P
西妥昔单抗
事件数 左侧 376(270) HR 中位 (95%CI) (95%CI) 36.0 (32.6-40.3) P
100 80 EFS (%) 60 40 20 0 0
Aug 27, 2012, and May 15, 2015， we screened 914 patients with KRAS exon 2 (codons 12 and 13) wild-type metastatic colorectal cancer and identified 48 (5%) patients with HER2-positive tumours, although two died before enrolment. Of these patients, 27 were eligible for the trial. All were evaluable for response. At the time of data cutoff on Oct 15, 2015, with a median follow-up of 94 weeks (IQR 51–127), eight (30%, 95% CI 14–50) of 27 patients had achieved an objective response, with one patient (4%, 95% CI −3 to 11) achieving a complete response, and seven (26%, 95% CI 9–43) achieving partial responses; 12 (44%, 95% CI 25–63) patients had stable disease
左侧肿瘤
发生率: ~60% 更年轻的患者 WT为主 预后较好
Lee MS, et al. 2016 ASCO Abstract 3506.
右侧肿瘤与抗EGFR PFS
基线特征
总体 (N=173) 中位年龄 男性 白人 右侧 MSI高表达 CIMP高表达 BRAF突变 NRAS突变 与化疗联合应用 二线/三线 58 62% 31% 7% 26% 17% 15% 92% 89%
19.4 右侧 293(242) (16.7-23.6)
1.55 <0.0001 (1.32-1.82)
100 80 EFS (%) 60 40 20 0
16.7 右侧 143(121) (13.1-19.4)
1.87 <0.0001 (1.48-2.32)
左侧 右侧
左侧 右侧
36 时间 (月)
72
OS
KRAS wt N=1025 所有患者 Cet BV
右侧 中位OS(月) 19.4 16.7 24.2
左侧 中位OS(月) 33.3 36.0 31.4
HR(95%CI)(校正) 1.55(1.32,1.82) 1.87(1.48,2.32) 1.32(1.05,1.65)
P(校正) <0.0001 <0.0001 0.01
晚期结直肠癌：内科治疗进展与困惑
301医院肿瘤内科 施伟伟
RAS 野生型mCRC 患者的OS更长
OPUS
1,2
FOLFOX FOLFOX + 西妥昔单抗
18.5 17.8 22.8 19.8 20.0 20.2 23.5 28.4 19.7 20.2 23.9 25.8 25.0 25.6
PRIME
5,6
FIRE-3 TRIBE
7,8
28.7 33.1 25.8 34.4 31.0 41.7 29.0 31.2 29.9 32.0
9,1 0
CALGB
11, 12
1. Bokemeyer. 2011; 2. Bokemeyer. 2014; 3. Van Cutsem. 2011; 4. Ciardiello. 2014; 5. Douillard. 2011; 6. Douillard. 2013; 7. Heinemann. 2013; 8. Stintzing. 2014; 9. Falcone. 2013; 10. Loupakis. 2014; 11. Venook. 2014; 12. Lenz. 2014.
KRAS RAS
CRYSTAL
3,4
FOLFIRI FOLFIRI + 西妥昔单抗 FOLFOX FOLFOX + 帕妥珠单抗 FOLFIRI + 贝伐珠单抗 FOLFIRI + 西妥昔单抗 FOLFIRI + 贝伐珠单抗 FOLFOXIRI + 贝伐珠单抗 化疗 + 贝伐珠单抗 化疗 + 西妥昔单抗