肺癌基因突变于化疗疗效分析

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ONTARIO CANCER INSTITUTE (OCI) PRINCESS MARGARET HOSPITAL
Objective:
To report the results of 2 important clinical trials reported at 2004 American Society of Clinical Oncologist
Phase II results suggested that in advanced NSCLC, vinorelbine plus cis-platinum yielded a 25-40% response rate.
Clinical question: Could vinorelbine and cisplatinum have adjuvant benefits for survival in stage IB and II NSCLC patients?
NCIC-CTG BR.10 Trial
Patients’ tumor and normal lung tissue collected in a paraffin block and frozen tumor bank and analysed for presence or absence of ras gene mutation
100
80
60 S ta g e I
40
S ta g e II
20
S ta g e IIIb S ta g e IIIa
S ta g e IV
0
12
24 36
48 60
M o n th s A fte r T re a tm e n t
Adenocarcinoma
100
80
60 S ta g e I
Clinical Stage
Percentage of Patients
I
36 %
~ 40%
II
8%
IIIA
10 %
IIIB
20 %
IV
27 %
5-year survival rate 60 % 39 % 23 % 5% <1 %
National Cancer Institute of Canada (NCIC-CTG BR.10 Trial)
A phase III prospective randomized study of adjuvant chemotherapy with
vinorelbine(长春瑞滨) and cisplatin(顺铂) in completely resected non-small cell lung cancer with companion tumor marker evaluation Principal Investigator: Dr. Tim Winton
Stomach
973 (9.5%)
835 (11.9%)
Liver
626 (6.1%)
611 (8.7%)
1999 WHO Pathological Classification of Lung Cancer
Non-small Cell Lung Cancer
Cumulative Proportion Surviving Cumulative Proportion Surviving
NCIC-CTG BR.10 Trial
Patients: Primary Tx:
T1N0, T1-2N1 Complete Surgical Resection
RANDOMIZATION
来自百度文库
Ras Analysis
Stratification:
Stage: N0 vs N1
Ras: absent vs. present vs. unknown
40 S ta g e II
20 S ta g e IIIa
S ta g e IV
S ta g e IIIb
0
12
24
36
48
60
M o n th s A fte r T re a tm e n t
Squamous cell carcinoma
NSCLC - Survival Rate and Proportion at Presentation vs. Clinical stage
Molecular pathology question: Could we identify molecular markers in the tumor tissue of these patients that can predict improvement in survival with or without adjuvant chemotherapy?
Incidence in thousands Deaths in thousands
(% total)
(% total)
Lung
1,305 (12.7%)
1,211 (17.2%)
Colon & rectum
Breast
1,045 (10.2%) 1,032 (10%)
608 (6.7%) 430 (6.1%)
Main message:
Molecular Pathology will soon be an important component of pathological diagnosis in lung cancer
World’s cancer incidence and cancer deaths
Observation alone
Chemotherapy
NCIC-CTG BR.10 Trial Tumor Banking
Patients’ tumor and normal lung tissue collected in a paraffin block and frozen tumor bank and analysed for presence or absence of ras gene mutation
Started in 1994 Completed in 2001
Results presented at ASCO 2004
NCIC-CTG BR.10 Trial
Early stage I and II NSCLC patients have an overall 5-year survival rate of 50%.
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