文档介绍：非小细胞肺癌治疗展望
吴一龙
广东省肺癌研究所
广东省人民医院
广东省医学科学院
Tarceva六周年庆/济南
Therapeutic Advances in the Last 5-10 Years
Biomarker-driven therapy for EGFR-mutant ALK-positive NSCLC
and targeted therapy
(EGFR TKIs & Crizotinib)
No
major advances
NSCLC
(Advanced Stage)
SCLC
(Limited & Extensive)
Unmet Needs to Advance Personalized Therapy in NSCLC
Recognition of lung plexity at the genomic level
-including inter- and intra patient tumor heterogeneity
Integration of this plexity into clinical decision-making process
NSCLC
(Early Stage)
No
major advances
Future
Patient B
versus
Patient A
Patient A
Homogeneous
Patient A
Heterogeneous
Patient A
Evolution
Patient A
Patient B
versus
Traditional
View
Inter-patient
Tumor Heterogeneity
Models for
Inter- and Intra-Patient Tumor Heterogeneity
Intra-patient
Tumor Heterogeneity
Evolution
over time
with
therapy
or
EGFR
MT+
ALK+
EGFR
MT+
EGFR MT-
Resistance
Mutation
T790M
Evolutionary Biology & Tumor Resistance
Intra-tumor heterogeneity is present at baseline
Reducing sensitive clones by therapy permits unopposed growth of less fit resistant clones
or emergence of a new clone (“Tumor Darwinism”)
Separating new “drivers” from emergent “passengers” is ing plex
Evolution
over time
with
therapy
“Driver”
Oncogene
New
“Driver”
Evolution
over time
with
therapy
“Driver”
Oncogene
New
“Driver”
Scenario 1
Scenario 2
from Gandara et al: Clin Lung Cancer, 2012
血液分子标志物研究:
更好的全貌,更容易的方法?
Detection of EGFR activating mutations from plasma DNA as a potent predictor of survival es in FASTACT 2 study: A randomized phase III study on bination of erlotinib (E) and chemotherapy (C)
Mok T, Wu YL et al ASCO 2013
-
EGFR 突变状态对治疗选择的影响
A phase II paring pemetrexed with gefitinib as the second-line treatment of non-squamous NSCLC patients with wild-type EGFR (CTONG0806)
EGFR Wild type
2nd line
Confirmed NSCLC
Pemetrexed
500mg/m, q3w
PD
Gefetinib 250mg qd
PD
N =157
Primary endpoint: PFS
Second endpoint: OS