第57回日本肺癌学会総会から
ランチョンセミナー１２
＜Advanced NSCLC without targetable driver mutation＞
１）two revolution in terms of advanced NSCLC treatment
1st revolution: EGFR mutation
IPASS study
From histological classification to genomic classification
sEGFRm 7%
ALKr 3%
BRAFm 2%
HER2 ?
KRASm 20%
Adenocarcinoma with no driver mutation 39%
Squamous cell carcinoma 26%
2nd revolution: Lung Cancer is also a disease of microenvironment
Precision Medicine
Reck et al, Lancet 2013
PD-L1 expression
２）chemotherapy
ECOG 1594 study
CDDP+PEM vs CDDP+GEM
Scagliotti et al, J Clin Oncol 2008
Ceppi et al, Cancer 2006
Vascular normalization with anti-VEGF therapy
VEGF-A targeted agent: bevacizumab, aflibercept
VEGFR 1-3 targeted agent: VEGFR-TKI
PDGFR targeted agent: nintedanib, ramcirumab
Patients selection reduced life threatening bleeding of bevacizumab therapy.
“ The duration of treatment “ issue
Strategy of post-treatment therapy
Platinum doublet→CR / PR / SD→PD→2nd line therapy
→CR / PR /SD→maintenance therapy
→PD→2nd line therapy
Maintenance therapy strategy
Meta-analysis, Behera et al, Lung Cancer 2012
フランスの現在の肺扁平上皮癌一次治療は、プラチナ併用化学療法＋necitumumab
フランスでは2nd Lineの選択肢が多い
DOC, PEM, Erotinib, afatinib
Nintedanib+DOC
Ramcirumab+DOC
REVEL study, Perol et al, ASCO2014 #8006
Ramcirumab phase II in Japan, Yoh et al, Lung Cancer 2016
Nivolumab, Pembrolizumab
CheckMate-017
Survival curves are crossing
→biomarkerが必要
Clinical factors: smoking status
Genomic expression profiling:KRAS, mutational load, neo-antigen
Expression of proteins: PD-1, PD-L1
Microenvironment: CD8(+)lymphocyte, T-reg, et al.
BluePrint study, Hirsch et al, J Thorac Oncol 2016
PD-L1 staining of tumor cells and immune cells
各種抗体ごとの評価、
Risk of early death in nivolumab (from CheckMate-057 study)
(PD-L1<10% non-Squamous NSCLC patients)
ICIs for 1st line setting
High PD-L1 expression→anti PD-L1 single agent
KEYNOTE-024 study
PD-L1 expression>50% patients can avoid chemotherapy toxicity
Intermediate PD-L1 expression→anti PD-L1 Ab and anti CTLA-4 Ab combined
Low PD-L1 expression→?
Driver mutationの有無:無ならfit for ICIs
PD-L1発現状態:highならfit for ICIs
Chemotherapy holiday:longならfit for ICIs
Cost
CBDCA+PEM+pembrolizumab phase II:PFS imoproved, OS not improved
