MOLEKULÁRIS DIAGNOSZTIKA KLINIKAI FELHASZNÁLÁSA ...€¦ · Analysis of KRAS/NRAS and BRAF...
Transcript of MOLEKULÁRIS DIAGNOSZTIKA KLINIKAI FELHASZNÁLÁSA ...€¦ · Analysis of KRAS/NRAS and BRAF...
MOLEKULÁRIS DIAGNOSZTIKA KLINIKAI FELHASZNÁLÁSA GASZTROINTESZTINÁLIS DAGANATOKBAN
Bodoky GyörgyDél-Pesti Centrum Kórház, Budapest
CRYSTAL study
Van Cutsem E, Bodoky G, Kyung Roh J et al. ECCO 2007
OPUS study
KRAS WT KRASM+
Bokemeyer C et al, ASCO 2008
Analysis of KRAS/NRAS and BRAF Mutations in the
Phase 3 PRIME Study of Panitumumab (pmab) +
FOLFOX vs FOLFOX as 1st-line Treatment (tx) for
Metastatic Colorectal Cancer (mCRC)
Kelly S. Oliner,1 Jean-Yves Douillard,2 Salvatore Siena,3 Josep Tabernero,4 Ronald Burkes,5 Mario Barugel,6 Yves Humblet,7 Gyorgy Bodoky,8 David Cunningham,9 Jacek Burkes, Mario Barugel, Yves Humblet, Gyorgy Bodoky, David Cunningham, Jacek
Jassem,10 Fernando Rivera,11 Ilona Kocákova,12 Paul Ruff,13 Maria Błasińska-Morawiec,14 Martin Šmakal,15 Richard Williams,1 Alan Rong,1 Jeffrey
Wiezorek,1 Roger Sidhu,1 and Scott Patterson1
1Amgen Inc., Thousand Oaks, California, USA; 2ICO René Gauducheau, Nantes, France; 3Ospedale Niguarda Ca’ Granda, Milan, Italy; 4Vall d’Hebron University Hospital, Barcelona, Spain; 5Mount Sinai Hospital, Toronto, Canada;
6Hospital de Gastroenterología, Buenos Aires, Argentina; 7Université Catholique de Louvain, Brussels, Belgium; 8Szent Laszlo Hospital, Budapest, Hungary; 9The Royal Marsden NHS Foundation Trust, London, United Kingdom; 10Medical
University of Gdansk, Poland; 11Hospital Universitario Marqués de Valdecilla, Santander, Spain; 12Masarykuv Onkologicky Ustav, Brno, Czech Republic; 13University of Witwatersrand Faculty of Health Sciences, Johannesburg,
South Africa; 14Wojewodzki Szpital Specjalistyczny, im. M. Kopernika, Lodz, Poland; 15Institut Onkologie a Rehabilitace na Plesi s.r.o., Nová Ves pod Pleší, Czech Republic
CONCLUSIONS
• In the wild-type RAS subgroup, a clinically significant 5.8 month improvement in OS (HR = 0.78, 95% CI: 0.62 - 0.99, p = 0.043) was observed in the panitumumab plus FOLFOX4 arm versus the FOLFOX4 alone arm
• Seventeen percent of patients had tumors that were wild-type KRAS exon 2/mutant in other RASexons
• Additional RAS mutations were negative predictive biomarkers in patients with mCRC treated with panitumumab plus FOLFOX4with panitumumab plus FOLFOX4
• BRAF mutations may not have been predictive of treatment effects and BRAF V600E mutations appeared to confer a poor prognosis regardless of treatment arm
• Panitumumab plus oxaliplatin-containing regimens should not be used in patients with mutant RAS mCRC tumors
• By excluding patients with mutant RAS mCRC tumors, the benefit-risk profile of panitumumab plus FOLFOX4 was improved and resulted in improvements in survival Oliner et al ASCO 2013
Could expanded RAS analysis change the results?
Presented By Josep Tabernero at 2014 ASCO Annual Meeting
Ritka driver mutációk jelentősége
79
107
37
GénTP53 47 % 39 %
KRAS 30 % 35 %
APC 40 % 30 %
PIK3CA 17 % 9 %
KRAS 34 % 46 %
TP53 59 % 37 %
APC 61 % 23 %
GénKRAS 71 % 75 %
TP53 44 % 50 %
CDKN2A 13 % 7 %
Gén
TP53 25 % 22 %
PIK3CA 9 % 8 %
CTNNB1 4 % 5 %
Gén
203 79203 79 107 37
28%
24%
22%
7%4%
[ÉRTÉ…
TP53
KRAS
APC
32%
30%
17%
5%15%
0 KRAS
TP53
50%34
%
5%4%8%KRAS
TP53
CDKN2A
42%16
%
42%
TP53
PIK3CA
egyéb
HER2 FISH pozitív 4 %
PIK3CA 17 % 9 %
BRAF 13 % 6 %
SMAD4 9 % 5 %
FBXW7 11 % 3 %
ATM 11 % 1 %
IDH1 2 % 1 %
NRAS 5 % 1 %
CDKN2A 2 % 1 %
CTNNB1 5 % 1 %
PIK3R1 4 % 1 %
GNAS 4 % 0,5 %
CHEK2 3 % 0,5 %
CDH1 3 % 0,5 %
KDR biomarker 23 %
PIK3R1 biomarker 8 %
APC 61 % 23 %
PIK3CA 8 % 8 %
FBXW7 12 % 5 %
BRAF 3 % 4 %
PTEN 4 % 1 %
SMAD4 10 % 1 %
AKT1 0,8 % 1 %
ATM 4 % 1 %
MET 1 % 1 %
PIK3R1 3 % 1 %
NRAS 8 % 1 %
HER2 FISH pozitív 3 %
KDR biomarker 25 %
PIK3R1 biomarker 9 %
CDKN2A 13 % 7 %
SMAD4 15 % 6 %
PIK3CA 2 % 4 %
APC 1 % 3 %
GNAS 5 % 1 %
CHEK2 0,1 % 1 %
EGFR 0,4 % 1 %
HER2 FISH pozitív 1 %
FGFR1 FISH pozitív 1 %
KDR biomarker 35 %
PIK3R1 biomarker 19 %
CTNNB1 4 % 5 %
KRAS 4 % 3 %
APC 4 % 3 %
PTEN 4 % 3 %
SMAD4 4 % 3 %
HER2 FISH pozitív 3 %
PIK3CA FISH pozitív 3 %
KDR biomarker 35 %
PIK3R1 biomarker 11 %
>5%2-5%
<2%
A colorectalis daganat heterogén betegség
CRC – az 50 leggyakrabban mutációt hordozó gén
2015, Foundation Medicine Inc.
Metasztatikus CRC: klinikailag potenciálisan releváns DNS alterációk
KRAS WT
KRAS amplificat
ion0.7%
METamplificat
ion2%
HER2amplification
3%BRAF 4.9%
KRAS exon 43.2%
NRAS exon 22.3%
NRAS exon 32.2%
NRAS exon 40.2%
Rutinban vizsgált
KRAS WT37.7%KRAS exon 3
2.5%
KRAS exon 241.4%
Misale S. et al.: Cancer Discov; 4(11) 1269–80. 2014 AACR.
vizsgált genetikai alterációk
Actionable targets in colorectal cancer
RAS:45%
OTHER:10%
PIK3CA:8%
PTEN:8%
HER-2:2%
BRAF 8%
PDGFRB:0,5%
GNAS:0,3
%
AKT1:0,3%
Alberto Bardelli, Ph.D.University of Torino, School of Medicine
MET:1%BRCA 1/2:2%
ALK-trsl:2%
EGFR:2%HER-4:1%
HER-3:1%
FEGFR:2%
CDK8 FISH+:4%
IGF2 FISH:4%
STK11:2%
JAK2:0,3
%FLT3:0,3%
KIT2:0,3%
A genetikai alterációk mindkét colonfélben jelen vannak
50
Pro
po
rtio
n o
f p
osi
tive
cas
es, %
40
30
20
CIMP-high
MSI-high
BRAF mutation
Pro
po
rtio
n o
f p
osi
tive
cas
es, %
10
0
Yamauchi. 2012
5045
2330
40
50
60
Bet
egek
szá
ma
Driver gének vastagbél adenocarcinomában203
58
145
8
23
14
3 1 10
10
20
30
0 1 2 3 4 5 7 9
Bet
egek
szá
ma
Egyes betegekben együttesen azonosított driver alterációk száma
Azon betegek száma, akik mintájában nem detektáltunk kódoló mutációtAzon betegek száma, akik mintájában legalább 1 kódoló mutációt detektáltunk
Stress signals DNA damage
PTEN
ATM
ATR
CHK2
CHK1p53
MDM2
P21
P16
Cdk4/6
Cyclin D1Rb EF2
TGFα
EGF
EGFR
HER2PI3K AKT mTOR
Driver gének vastagbél adenocarcinomában
FBXW7
NICD1
Cyclin E 203
PM
39%0,5%
1%(PIK3R1)
1% (CDKN2A)
1%
3%
9%(PIK3CA)
4% (FISH)
EGF
HGF
FGF
PGE20
WNT
HER2
MET
FGFR
GPCR
Frizzled
ECAD
RAS RAF MEK ERK
αs AC cAMP PKA
APC
β-catenin
Dvl GSK-3β
β-catenin
Axin
TGFβ TGFβR I/II Smad2/3Smad4
isocitrate IDH1 α-KGHistone and DNA methylation
0,5%(CDH1)
0,5% (GNAS)
1% (CTNNB1)
1%(NRAS)
1%5%
6%(BRAF)
30%
35%(KRAS)
onkogéntumorszupresszor
aktiválásgátlás
kapcsolódásplazmamembrán
apoptózisproliferáció
driver gén
% Adott gént érintő driver mutációk aránya a vizsgált betegekben
79
Driver gének végbél adenocarcinomában
23
17
1115
20
25
Bet
egek
szá
ma
20
59
3
11
3 2
0
5
10
0 1 2 3 4 5
Bet
egek
szá
ma
Egyes betegekben együttesen azonosított driver alterációk száma
Azon betegek száma, akik mintájában nem detektáltunk kódoló mutációtAzon betegek száma, akik mintájában legalább 1 kódoló mutációt detektáltunk
Stress signals DNA damage
PTEN
ATM
ATR
CHK2
CHK1p53
MDM2
P21
P16
Cdk4/6
Cyclin D1Rb EF2
TGFα
EGF
EGFR
HER2PI3K AKT mTOR
FBXW7
NICD1
Cyclin E 79
Driver gének végbél adenocarcinomábanPM
1%(PIK3R1)
1%
1%
1%
5%
8%(PIK3CA)
37%
3% (FISH)
EGF
HGF
FGF
PGE20
WNT
HER2
MET
FGFR
GPCR
Frizzled
ECAD
RAS RAF MEK ERK
αs AC cAMP PKA
APC
β-catenin
Dvl GSK-3β
β-catenin
Axin
TGFβ TGFβR I/II Smad2/3Smad4
isocitrate IDH1α-KG
Histone and DNA methylation
1%(NRAS)
1%
1%
1%
4%(BRAF)
23%
46%(KRAS)
3%
Primary resistance to anti-EGFR therapy in colorectal cancer
Responder WT: 15%
K-NRAS: 35-45%
BRAF: 5-10%
PIK3CA/PTEN: 15%
NR 4xWT = 20%
KRAS FISH+: 1%
HER-2 FISH+: 3%
MET FISH+: 2%
Alberto Bardelli, Ph.D.University of Torino, School of Medicine
BRAF M+5%
PIK3CA M+10%
EGFR-DRIVEN COLON CC
20-25%(EGFR CNG, +LIGANDS)
NRAS 2,3,4 M+ 10%HER-2 M+
5%
ALK/EML!2,5%
MET+5-10%
KRAS 2,3,4 exons M+ 10%
KRAS 1 exons M+ 35-40%
TARGETS in colorectal cancer
Panitumumab
Cetuximab
Cetuximab, PanitumumabNecitumumab, Neratinib
MEK: Pimasertib, Trametinib, SelumetinibNOTCH: demcizumab, MK-0752CDK9: AZD5438, dinaciclib, BAY1000394PLK1: volaserib, GSK-461364
TrastuzumabLapatinibNeratinibAfatinib
CrizotinibAMG 337TivantinibForetinib
vemurafenib
everolimus
BRAF M+5%
PIK3CA M+10%
EGFR-DRIVEN COLON CC
10-20%(EGFR CNG, +LIGANDS)
NRAS 2,3,4 M+ 10%HER-2 M+
5%
ALK/EML!2,5%
MET+5-10%
KRAS 2,3,4 exons M+ 10%
KRAS 1 exons M+ 35-40%
Primary resistance to anti-EGFR therapy in colorectal cancer
EGFR Inhibitors NO EGFR InhibitorsEGFR Inhibitor is possible but increased risk of resistance!
HUNTING DRIVERS (EGFR DEPENDENCE BY ACTIVATION)
KRAS/NRAS/BRAF/PIK3CA WT COLON CC LIVER MET CETUXIMAB
EGFR MABS IN BRAF MUTANT COLON CC
Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, Bardelli A. J Clin Oncol. 2008 Dec 10;26(35):5705-12.
FOLFOXIRI+BEVACIZUMAB IN BRAF MUTANT COLON CC
N FOLFIRI +bev
median OS
FOLFOXIRI + bev
median OS
HR [95% CI] p
RAS and BRAF wt
93 33.5 41.7 0.77 [0.46-1.27]
0.522 *RAS
mutated236 23.9 27.3 0.88
[0.65-1.18]
BRAF
mutated28 10.7 19.0 0.54
[0.24-1.20]
* p for interaction
Cremolini et al., Lancet Oncol 2015
Melanoma: vemurafenib, dabrafenib-trametinib
NSCLC: vemurafenib, dabrafenib
Papilláris pajmirigy daganat: vemurafenib
BRAF-V600E
Hajas sejtes leukémia: vemurafenib
Cholangiocarcinoma: dabrafenib+trametinib
Vastagbél adenokarcinoma: ?
BRAF+EGFR
BRAF GÁTLÓK HATÉKONYSÁGA VASTAGBÉLDAGANATOKBAN
BRAF
Yan Y, Grothey A. Molecular profiling in the treatment of colorectal cancer:focus on regorafenib. Onco Targets Ther. 2015 Oct 15;8:2949-57.
BRAF+EGFR+MEK
BRAF+EGFR+irinotecan
BRAF+EGFR+PIK3CA
Randomized trial of irinotecan and cetuximab
with or without vemurafenib in BRAF-mutant
metastatic colorectal cancer (SWOG S1406)
Scott Kopetz, 1 Shannon McDonough, 2 Heinz-Josef Lenz, 3 Anthony Magliocco, 4 Chloe Atreya,5 Luis A. Diaz Jr., 6 Carmen Allegra,7 Kanwal Raghav,1 Van Morris,1 Stephen Wang, 8 Christopher Lieu, 9
Katherine A. Guthrie, 2 Howard S. Hochster10Katherine A. Guthrie, 2 Howard S. Hochster10
1The University of Texas MD Anderson Cancer Center, Houston, TX; 2Fred Hutchinson Cancer Research Center, Seattle, WA; 3USC Norris Comprehensive Cancer Center, Los Angeles, CA; 4H. Lee Moffitt Cancer
Center & Research Institute, Tampa, FL; 5University of California, San Francisco, San Francisco, CA; 6Memorial Sloan Kettering Cancer Center, NewYork, NY; 7University of Florida, Gainesville, FL; 8Kaiser
Permanente, Sacramento, CA; 9University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO; 10Yale Cancer Center, New Haven, CT
Secondary Endpoint: Overall Survival
HR = 0.73 (95% CI 0.45 – 1.17)P=0.19
80%
100%
60%
N Events Median 95% Conf IntCetuximab + Irinotecan 50 38 5.9 (3.0 – 9.9)Vemurafenib + Cetuximab 49 32 9.6 (7.5 – 13.1)
+ Irinotecan
0 3 6 9 12 15 18Months after randomization
40%
20%
0%
April 18. 2017 data cutoff
Presented by: Scott Kopetz, MD, PhD
MULTICENTRIKUS VIZSGÁLAT BRAF MUTÁNS VASTAGBÉLDAGANATOKBAN ÚJ GENERÁCIÓS BRAF ÉS MEK GÁTLÓKKAL
BRAFi+cetuxumab
BRAFi+MEKi+cetuxumab
FOLFIRI+cetuximab
1L cetuximab-FOLFIRI, PR liver resection in 16APR2012, the 1L therapy was continued (until OCT2013), 2L FOLFOX, then panitumumab-FOLFOX (RFTS: CR in OCT2014),right upper lung lobe VATS resection in 07APR2015, 3L bevacizumab-FOLFIRI (from 28JUL2015 until 09FEB2016, PD),
FIGHTING SECONDARY RESISTANCE: HER-2
3L bevacizumab-FOLFIRI (from 28JUL2015 until 09FEB2016, PD), HER-2 amplification 4L afatinib (from JUL2016 until 12SEP2016, PD), 5L regorafenib (2x, PD), 6L tegafur, 7L metronomic capecitabine, Antwerp University lapatinib/trastuzumab (compassionate)
FIGHTING SECONDARY DRUG RESISTANCE: Secondary mutant KRAS canbe detected after progression on EGFRi but mKRAS levels drop during EGFRi holiday
Nat Med. 2015 July ; 21(7): 795–801. doi:10.1038/nm.3870.
3511 Parseghian. Anti-EGFR resistant clones decay exponentially after progression:Implications for anti-EGFR rechallenge <br />
Presented By Alberto Sobrero at 2018 ASCO Annual Meeting
Slide 12
Presented By Alberto Sobrero at 2018 ASCO Annual Meeting
My take
Presented By Alberto Sobrero at 2018 ASCO Annual Meeting
EGFR
HER-2
20% IHC+0% M+7% CNG
IGFR
C-MET IHC+ 70%
FGFR
ALK/EML4
70-90% (M+) RON
5% M+0% CNG
AMPEPI
HGF
IHC+ 40%
IGFI
CrizotinibCabozantinib
XL184
Erlotinib
²¹²Pb-TCMC-TrastuzumabTrastuzumab, lapatinib , TDM-1
AMG 479
Dovitinib
FGFRvIIIb
FGFRvIIIc
Drugable driver genes in pancreatic cancer
KRAS
BRAF
MEK
AKT/PKB
PIK3CA
MTOR
70-90% (M+)
2% (M+)
1% (M+)
8% (M+)
3% (M+)
PTEN
RON
NRASHRAS1% (M+)
INSRA/B
IGFII
INS
NOTCH
G-SECRETASE
Trametinib, AS703026BAY 86-9766, AZD6244
MRK003
PLK1VolasertibTAK-960
Naflivir GDC-0980 Metformin, everolimus
vemurafenibVismodegibVismodeglib
SMO
CDK4
BKM120
PalbociclibBAY1000394AZD5438
CDKN2A91% (M+)
P53
MDM2
84% (M+)SMAD4 50%(M+)
Clinical Significance of the Genetic Landscape of Pancreatic Cancer
1% 18% 44% 37%
Yachida S, et al.. Clinical significance of the genetic landscapeof pancreatic cancer and implications for identification of potential long-term survivors.
Clin Cancer Res. 2012 Nov 15;18(22):6339-47.
OS= 9 months (p=0,04)OS= 24 months
PIK3CA M+5%
EGFR 5-10%
C-MET-HGF AUTOCRINE LOOP 40%HER-27-20%
AKT 3%
PIK3CA CNG?%
PTEN M+?%
Platform trial design in pancreatic cancer
KRAS M+ (70-90%)
ERLOTINIB
HER-2 INH
AKTINH
PI3K/MTOR inhibitor
PLK1, CDK4, NOTCH, MEK, MET INHIBITOR
107
Driver gének hasnyálmirigy adenocarcinomában
32
42
30
40
50
Bet
egek
szá
ma
13
94
710
2 10
10
20
0 1 2 3 4 5
Bet
egek
szá
ma
Egyes betegekben együttesen azonosított driver alterációk száma
Azon betegek száma, akik mintájában nem detektáltunk kódoló mutációtAzon betegek száma, akik mintájában legalább 1 kódoló mutációt detektáltunk
Stress signals DNA damage
PTEN
ATM
ATR
CHK2
CHK1p53
MDM2
P21
P16
Cdk4/6
Cyclin D1Rb EF2
TGFα
EGF
EGFR
HER2PI3K AKT mTOR
FBXW7
NICD1
Cyclin E 107
Driver gének hasnyálmirigy adenocarcinomábanPM
1%
1% (FISH)
4%(PIK3CA)
7% (CDKN2A)
50%
EGF
HGF
FGF
PGE20
WNT
HER2
MET
FGFR
GPCR
Frizzled
ECAD
RAS RAF MEK ERK
αs AC cAMP PKA
APC
β-catenin
Dvl GSK-3β
β-catenin
Axin
TGFβ TGFβR I/II Smad2/3Smad4
isocitrate IDH1α-KG
Histone and DNA methylation
1% (FGFR1 FISH)
1% (GNAS) 3%
6%
75%(KRAS)
EGFR
HER-2
1,8% M+
25% FISH+
KIT 2% M+
C-MET
1% M+, 15% FISH+
FGFR
0,8% M+
4,1% FISH+
ALK/EML4
PDGFR
4% M+
5% FISH+
Drugable driver genes in gastric cancer
KRAS
BRAF
MEK
AKT/PKB
PIK3CA
MTOR
6,5% M+
1,1% M+
1% M+
8% M+
67% FISH+
3,8% M+PTEN
PDGFR
HRASNRAS
Driver gének gyomor adenocarcinomában37
14
11
8
10
12
14
16
Bet
egek
szá
ma
9
28
21
0
2
4
6
8
0 1 2 4
Bet
egek
szá
ma
Egyes betegekben együttesen azonosított driver alterációk száma
Azon betegek száma, akik mintájában nem detektáltunk kódoló mutációtAzon betegek száma, akik mintájában legalább 1 kódoló mutációt detektáltunk
Stress signals DNA damage
PTEN
ATM
ATR
CHK2
CHK1p53
MDM2
P21
P16
Cdk4/6
Cyclin D1Rb EF2
TGFα
EGF
EGFR
HER2PI3K AKT mTOR
Driver gének gyomor adenocarcinomábanFBXW7
NICD1
Cyclin E 37PM
3%8%(PIK3CA)
22%
3% (FISH)
EGF
HGF
FGF
PGE20
WNT
HER2
MET
FGFR
GPCR
Frizzled
ECAD
RAS RAF MEK ERK
αs AC cAMP PKA
APC
β-catenin
Dvl GSK-3β
β-catenin
Axin
TGFβ TGFβR I/II Smad2/3Smad4
isocitrate IDH1α-KG
Histone and DNA methylation
3%
3%
3%(KRAS)
5% (CTNNB1)
Wil type; 1only
polymophism
; 13 mutacions;
2
4+ mutacions;
1
16,67%
Most frequently mutated driver genes in gastric cancers (N=16, 58 genes tested)
1 mutacion; 42 mutacions;
3
83,34
%
5
6
Distribution of all mutations in gastric cancers
1 1 1 1 1 1 1 1 1
EGFR +„szuper wt” and
FISH+/M+PIK3CA-/MET-
/HER-2-C-MET +
(FISH+/M+)
HER-2 +PIK3CA-/MET -
PIK3CA + (FISH+/M+/PTEN M+)
FGFR FISH+PIK3CA -
Platform trial design in gastric cancer
LapatinibNeratinibAfatinib
AZD4547DovitinibPonatinib
nintedanib
CrizotinibAMG 337TivantinibForetinib
ErlotinibGefitinib
CetuximabPanitumumabNecitumumab
Neratinib
EverolimusMetforimn
TemsirolimusXL147
BKM120BEZ235
TARGETING PARP IN HOMOLOGEUS RECOMBINATION DEFICIENT (HRD) TUMORS
John L. Marshall, MD Chief, Division of Hematology/OncologyGeorgetown University Hospital Director, Otto J. Ruesch Center for the Cure of Gastrointestinal Cancer Washington, DC
Patient case
• A 72-yr-old male presents with abdominal pain, jaundice– CT scan shows a pancreas head mass and several small liver
lesions
• Biopsy of the liver positive for adenocarcinoma c/w pancreas cancerpancreas cancer– Family history: mother and maternal aunt with ovarian
cancer– Patient is of Ashkenazi Jewish heritage
• Biliary stent placed; patient eager to start treatment
a) Start standard chemotherapy?
b) Order molecular profiling?
Patient Case
• Tumor biopsy sent for molecular profile and was positive for a BRCA mutation
• Patient enrolled on a trial of FOLFOX + veliparib• Patient enrolled on a trial of FOLFOX + veliparib
• Achieved CR, in response for 26 mos
PDL-1 és MSI hazai GI betegekben
MSI vizsgálatPD-L1 expresszió vizsgálat
100%
0%
Epeúti daganatn=8
95%
5%
Hasnyálmirigydaganat n=21
87%
13%
Epeúti daganat
85%
15%
Hasnyálmirigy daganatn=8 n=13
FDA: PEMBROLIZUMAB
MSS MSI-H MSS MSI-H
90%
10%
Gyomor daganat
MSS MSI-H
97%
3%
Vastag- és végbéldaganat
MSS MSI-H
n=99 n=10
PD-L1 negatív PD-L1 pozitív PD-L1 negatív PD-L1 pozitív
86%
14%
Vastag- és végbéldaganat
PD-L1 negatív PD-L1 pozitív
93%
7%
Gyomor daganat
PD-L1 negatív PD-L1 pozitív
n=7 n=15
EVER TRIED.EVER TRIED.EVER FAILED.EVER FAILED.NO MATTER.NO MATTER.TRY AGAIN.TRY AGAIN.TRY AGAIN.TRY AGAIN.FAIL AGAIN.FAIL AGAIN.FAIL BETTER.FAIL BETTER.
Samuel Beckett