(EGFR) mutations

EGFR e meccanismi di
resistenza agli inibitori
Marcello Tiseo
U.O. Oncologia Medica
Azienda Ospedaliero-Universitaria di Parma
Mutazioni di EGFR e TKIs:
punti fermi


Netto impatto dei trattamenti in OS: 2-3 anni
8 studi random di I linea vs CT
- TKI > CT in RR (60-70%), PFS (9-13 mesi), tossicità

3 TKIs in I linea (2 rev e 1 irr)
- non disponibili confronti diretti di fase III



Efficacia in qualunque linea di terapia
Tossicità peculiari
Instaurarsi di resistenza:
- differenti meccanismi e diverse potenziali strategie
Mutazioni di EGFR e TKIs:
quesiti aperti





Quale il “migliore” TKI in I linea
Circa 30% dei pazienti mutati non risponde a TKI
Scarsa conoscenza in caso di mutazioni
“uncommon” e in caso di combinazione di diverse
mutazioni
Non chiara efficacia in caso di T790M de novo
Non chiara definizione della terapia alla
progressione a TKI
Mutazioni di EGFR e TKIs:
quesiti aperti





Quale il “migliore” TKI in I linea
Circa 30% dei pazienti mutati non risponde a TKI
Scarsa conoscenza in caso di mutazioni
“uncommon” e in caso di combinazione di diverse
mutazioni
Non chiara efficacia in caso di T790M de novo
Non chiara definizione della terapia alla
progressione a TKI
Mutations in the EGFR gene
Confer sensitivity/resistance to EGFR
TKIs
EGFR transcript
Unclear effect on sensitivity to
EGFR TKIs
P694X
18
Extracellular
domain
Exons 1–16
EGFR
D761Y
Exons 18–24
Exons 25–28
18
20
T790M
L858R
Regulatory
domain
19
L730F P733L
E746K
Exon 17
D770_N771 insNPG
Tyrosinekinase
domain
E709X
G719A/S
Deletions
Transmembrane
domain
V700D
L861X
21
A763V
N765A
S768I
T783A
L792P
L798F
G810S
N826S
L838V
T847I
I853T
A859T
G735S
V738F V742A
T751I
S752Y
D761N
L833V
H835L
H850N
V851X
G863DA864T
E866K
TKI = tyrosine-kinase inhibitor
Riely, et al. Clin Cancer Res 2006
Activity of afatinib in uncommon epidermal growth
factor receptor (EGFR) mutations: Findings from
three prospective trials of afatinib in EGFR mutationpositive lung cancer
J. C.-H. Yang1, L.V. Sequist2, S. L. Geater3, C.-M. Tsai4, T. Mok5, M. H. Schuler6,
N. Yamamoto7, D. Massey8, V. Zazulina8, Yi-Long Wu9
1National
Taiwan University Hospital, Taipei, Taiwan; 2Massachusetts General Hospital, Boston, MA, USA;
of Respiratory and Respiratory Critical Care Medicine, Department of Internal Medicine, Faculty of Medicine,
Prince of Songkla University, Songkhla, Thailand; 4Taipei Veterans General Hospital, Taipei, Taiwan;
5The Chinese University of Hong Kong, Hong Kong; 6West German Cancer Center, University Duisburg-Essen, Essen, Germany; 7Shizuoka
Cancer Center, Shizuoka, Japan; 8Boehringer Ingelheim Limited, Bracknell, UK; 9Guangdong Lung Cancer Institute, Guangdong General Hospital
and Guangdong Academy of Medical Sciences, Guangzhou, China
3Division
LUX-Lung clinical trials and eligibility
LUX-Lung 2
LUX-Lung 3
LUX-Lung 6
Phase II
Phase III
Phase III
N=129
N=345
N=364
Afatinib
Afatinib vs.
Pemetrexed/
cisplatin
Afatinib vs.
Gemcitabine/
cisplatin
Line of
treatment
First- and secondline (after chemo)
First-line
First-line
Mutation
test
Direct sequencing
(central)
EGFR29* (central)
EGFR29* (central)
Treatment
*EGFR mutations detected by TheraScreen EGFR29 test:
– Common: 19 deletions in exon 19 and L858R in exon 21
– Uncommon: 3 insertions in exon 20, L861Q, T790M, G719S, G719A and G719C, S768I
EGFR mutation-positive patients in LUX-Lung trials
LUX-Lung 2
LUX-Lung 3
LUX-Lung 6
Phase II
Phase III
Phase III
N=129
N=345
N=364
Del19
n=408
n=52
n=170
n=186
L858R
n=330
n=54
n=138
n=138
Uncommon
n=100
n=23
n=37
n=40
Patients with uncommon mutations treated with afatinib
Uncommon
n=75
n=23
n=26
n=26
Subgroups of patients with uncommon mutations
Categories
n= 75
Mutations
(n)
De novo
T790M
Exon 20
insertions
Other
(exon 18, 19, 20, 21)
14
23
38
T790M alone (3)
T790M+Del19 (3)
T790M+L858R (6)
T790M+G719X (1)
T790M+L858R+G719X (1)
n/a
L861Q alone (12)
G719X alone (8)
G719X+S768I (5)
G719X+L861Q (3)
E709G or V+L858R (2)
S768I+L858R (2)
S768I alone (1)
L861P alone (1)
P848L alone (1)
R776H+L858R (1)
L861Q+Del19 (1)
K739_1744dup6 (1)
Total analyzed
T790M+
Exon 20 insertion
Other
838
1.6%
2.7%
4.5%
Outcome in patients with uncommon mutations
120
Maximum change from baseline (%)
100
De novo T790M (n=14):
T790M alone, T790M+Del19, T790M+L858R, T790M+G719X, T790M+L858R+G719X
80
60
Exon 20 insertions (n=20)
40
L861Q, G719X, G719X+S768I, G719X+L861Q, E709G or V+L858R, S768I+L858R,
S768I, L861P, R776H+L858R, L861Q+Del19, K739_1744dup6
Other (n=33):
20
0
-20
-40
T790M
Exon 20 ins
Other
Response rate (%)
14.3
8.7
71.1
DCR (%)
64.2
65.2
84.2
PFS (months)
2.9
2.7
10.7
OS (months)
14.9
9.4
18.6
-60
-80
-100
Istituto Toscano Tumori-Livorno-Italy
How afatinib compares to reversible EGFR-TKIs
in presence of uncommon EGFR mutations?
Reversible EGFR-TKIs1
Afatinib 2,3,4
EGFR
N
RR
(%)
PFS
(months)
OS
(months)
N
RR
(%)
PFS
(months)
OS (months)
Exon 19-21
278
74.1
8.5
19.6
3084
60.8
13.6
-
Wild-type
272
16.5
2.0
10.4
423
0
1.0
7.2
Exon 20
insertion
11
0
1.4
4.8
202
8.7
2.7
9.4
G719
15
53.3
8.1
16.4
182
78.0
13.8
26.9
L861
15
60.0
6.0
15.2
162
56.0
8.2
16.9
Other
15
20.0
1.6
11.1
1
100
-
-
1Wu
J et al. Clin Cancer Res 2011; 2Yang Y et al. WCLC 2013; 3 Ahn et al, ESMO 2012; 4Sequist et al JCO 2013
Mutazioni Uncommon
Yang et al: considerazioni





Il più grande data set prospettico sulle mutazioni
uncommon, trattate in modo omogeneo
Conferma che costituiscono circa 10% delle
mutazioni di EGFR
Gruppo eterogeneo
Efficacia modesta in caso di inserzione del 20 e
T790M de novo degli attuali EGFR TKIs
Efficacia contro altre mutazioni uncommon
(G719, L861) simile alle comuni e simile fra TKIs
Mutazioni Uncommon
Yang et al: considerazioni





Il più grande data set prospettico sulle mutazioni
uncommon, trattate in modo omogeneo
Conferma che costituiscono circa 10% delle
mutazioni di EGFR
Gruppo eterogeneo
Efficacia modesta in caso di inserzione del 20 e
T790M de novo degli attuali EGFR TKIs
Efficacia contro altre mutazioni uncommon
(G719, L861) simile alle comuni e simile fra TKIs
Clinical, structural and biochemical
characterization of epidermal growth
factor receptor (EGFR) exon 20 insertion
mutations in lung cancer
Hiroyuki Yasuda, MD1*; Eunyoung Park, PhD2*; Cai-Hong Yun, PhD6*; Natasha J. Sng, MS1; Wee-Lee Yeo,
MD1; Antonio R. Lucena-Araujo, PhD1; Sohei Nakayama, MD1; Kota Ishioka, MD1; Mark S. Huberman,
MD1; David W. Cohen, MD1; Norihiro Yamaguchi, MD, MPH1; Megan Hanna, PhD2; Geoffrey R. Oxnard,
MD2; Christopher S. Lathan, MD, MPH2; Teresa Moran, MD3; Lecia V. Sequist, MD, MPH3; Jamie E. Chaft,
MD4; Gregory J. Riely, MD, PhD4; Maria E. Arcila, MD4; Ross A. Soo, MBBS5; Matthew Meyerson, MD,
PhD2; Michael J. Eck, MD, PhD2#; Susumu S. Kobayashi, MD, PhD1#; Daniel B. Costa, MD, PhD1#
1
Beth Israel Deaconess Medical Center, 2 Dana-Farber Cancer Institute, 3 Massachusetts General Hospital, all at Harvard Medical School, Boston, MA, USA; 4 Memorial
Sloan Kettering Cancer Center, New York, NY, USA; 5 National University Cancer Institute, National University of Singapore, Singapore; and 6 Peking University Health
Science Center, Beijing, China
Funding source:
Daniel B. Costa, MD, PhD, MMSc
Division of Hematology/Oncology
BIDMC
WCLC 2013 (October 29th 2013)
ABSTRACT # 747
MO16 - Prognostic and Predictive Biomarkers IV
EGFR exon 20 insertion mutations:
cluster within or following the regulatory C-helix of EGFR and most, outside
A763_Y764insFQEA, are insensitive to reversible EGFR TKIs
N-lobe
exon 18
G719S
exon 21
L858R
L861Q
H773_V774insH
sensitive
exon 20
insertions
D770_N771insNPG
D770_N771insSVD
exon 19
deletions
762 763 764 765 766 767 768 769 770 771 772 773 774
A767_V769dupASV
sensitive
C-helix
M766_A767insAI
exon 18
G719X
exon 19
deletions
Y764_V765insHH
in vitro
sensitivity to
EGFR TKIs
(erlotinib or
gefitinib)
A763_Y764insFQEA
EGFR
mutation
type
loop following C-helix
exon 19
insertions
sensitive
exon 20
A763_Y764
insFQEA
sensitive
exon 20
insertions
(others)
resistant
exon 20
T790M
resistant
exon 21
L858R
sensitive
exon 21
L861Q
sensitive
C-lobe
EGFR exon 20 insertion mutated non-small-cell lung cancers (NSCLC):
All tumors, outside EGFR-A763_Y764insFQEA-bearing ones, displayed lack of
objective radiographic or clinical responses to reversible EGFR TKIs (gefitinib and
erlotinib) in a retrospective review of five academic medical centers in the United
States and Singapore
Best response to reversible EGFR TKI
*
EGFR mutation
drug
PR
SD
PD
RR [%]
A763_Y764insFQEA
erlotinib
2
1
-
66.6%
Y764_V765insHH
gefitinib
-
1
-
0%
M766_A767insASV
erlotinib
-
-
1
0%
A767_V769dupASV
gefitinib
-
-
1
0%
V769_D770insASV
erlotinib
-
-
1
0%
D770_N771insGL
erlotinib
-
-
2
0%
D770_N771insGT
erlotinib
-
-
1
0%
D770_N771insSVD
erlotinib
-
1
1
0%
delD770insGY
erlotinib
-
-
2
0%
P772_H773insYNP
gefitinib
-
-
1
0%
P772_V774insPHV
erlotinib
-
-
1
0%
H773_V774insH
gefitinib/
erlotinib
-
-
2
0%
H773_V774insNPH
erlotinib
-
-
1
0%
Implications of the crystal structure of typical EGFR exon 20 insertion:
Crystal structure of D770_N771insNPG (insNPG). The inserted residues form a “wedge” at the end
of the C-helix that may effectively lock the helix in its inward, active position. Structure and enzyme
kinetic studies, shows that this insertion mutant binds EGFR TKIs with a binding mode and apparent
affinity similar to that of wild-type (WT) EGFR
Progression-free survival according to
treatment group and T790M mutation status
G1: Erlotinib and T790M present (n=34)
G2: Erlotinib and T790M absent (n=16)
G3: Chemotherapy and T790M present (n=28)
G4:Chemotherapy and T790M absent (n=17)
G2
G4
5·1
6·0
9·7
15·8
G3
G1
Patients at risk
Rosell et al, Poster WCLC 2013
15th World Conference on Lung Cancer
Prognostic and Predictive Biomarkers V
Sydney, 30 October 2013
Pretreatment evaluation of T790M mutation and its
correlation with response to tyrosine kinase
inhibitors (TKIs) or chemotherapy in advanced nonsmall cell lung cancer (NSCLC) patients with
activated EGFR mutations
Francesco Grossi, Maria Giovanna Dal Bello, Erika Rijavec, Claudio Sini, Carlo
Genova, Giulia Barletta, Carlotta Defferrari, Simona Coco, Anna Truini, Angela
Alama, Simona Zupo, Mariella Dono
Lung Cancer Unit
National Institute for Cancer Research
Genova, Italy
Selection of patients and samples
363
Tested for EGFR mut
305 (84 %)
EGFR WT
58 (16 %)
EGFR MUT
RT-PCR
Sanger sequencing
4* (6.9 %)
54 (93.1 %)
T790M +
T790M -
*2 pts ineligible: 1 second primary tumor,
1 treatment data not available (second
opinion)
42 (77.7 %)
12 (22.2 %)
LNA-PCR/Sanger sequencing
Insufficient tissue
17 (40.5%)
25§(59.5 %)
T790M +
T790M -
19
23
T790M+
T790M-
§2 pts ineligible: early stages
PFS* & OS according to
the EGFR T790M status
…. T790M
mutated Median PFS= 8.55 months
__ T790M wild-type Median PFS= 7.99 months
*First-line PFS
…. T790M
__ T790M
mutated Median OS= 32.23 months
wild-type Median OS= 22.99 months
RR and PFS to first-line treatment
with EGFR TKIs or CT
RR and PFS to first treatment with
afatinib or erlotinib/gefitinib
EGFR T790M de novo:
considerazioni





Con metodiche più sensibili percentuale più
elevata (da circa 4-5% a 40%)
Arterfatto in paraffina, non in frozen? High
T790M detection rate in TKI-naïve, Truth or
Artifact ? Ye et al, JTO 2013
Probabilità di risposta a TKI inferiore
Pazienti con buona prognosi
Quale la migliore strategia? TKI o CT come
prima linea? Quale TKI?
Meccanismi di resistenza
a EGFR-TKIs
Clinical EGFR Inhibitors
Drug
Stage
Covalent
Overcome T790M
Gefitinib
Structure
Approved
No
No
Quinazoline
Erlotinib
Approved
No
No
Quinazoline
Dacomitinib
Phase III
Yes
No
Quinazoline
Afatinib
Approved
Yes
No
Quinazoline
AP26113
Phase I/II
No
?
Pyrimidine
CO-1686
Phase I
Yes
Yes
Pyrimidine
AZD9291
Phase I
Yes
Yes
Pyrimidine
Third generation compounds selectively target EGFR T790M
They are 30- to 100-fold more potent against EGFR T790M and up to 100-fold less potent
against WT EGFR than quinazoline-inhibitors
Janne, Mini Symposium MS27, WCLC 2013
Nuovi farmaci alla resistenza:
CO-1686 e AZD9291
First-In-Human Evaluation of CO-1686, an Irreversible,
Highly Selective Tyrosine Kinase Inhibitor of Mutations of
EGFR (Activating and T790M)
Soria et al
AZD9291: an irreversible, potent and selective tyrosine
kinase inhibitor (TKI) of activating (EGFR+) and resistance
(T790M) mutations in advanced NSCLC. The AURA study
Ranson et al
CO-1686 generates complete responses in
L858R/T790M transgenic model
CO-1686: Baseline
Afatinib : 3W
CO-1686: 3W
C h a n g e f r o m B a s e lin e (% )
Afatinib: Baseline
600
400
200
L 8 5 8 R /T 7 9 0 M
100
T ra n s g e n ic M o d e l
80
PD
60
40
20
0
SD
-2 0
-4 0
PR
-6 0
-8 0
CR
-1 0 0
A f a tin ib
C O -1 6 8 6
2 0 m g /k g
5 0 m g /k g B ID
Afatinib dosed at MTD - potency limited by WT EGFR inhibition
67% RECIST response rate in evaluable T790M+ patients
treated at 900mg BID
8 of 9 patients progressed on TKI immediately prior to CO-1686
Number of Previous
EGFR TKI lines
1
2
2
2
4
2
2
*
*
*
*
18
11
8
1
1
*
6
*
*
*
*
22
15
24
EGFRi immediately before CO-1686
*
21
30
Weeks on treatment
Classical AEs observed with WT-EGFR
inhibition uncommon with CO-1686
% patients with event
Comparator data from US prescribing information
In vitro and In vivo activity of AZD9291
•
AZD9291 is a potent oral,
irreversible inhibitor of
EGFR that contains EGFRTKI-sensitising (EGFR+)
and resistance mutations
(T790M)
•
Good potency and high
selectivity demonstrated in
enzymatic and cellular in
vitro assays1
Model
AZD9291
phospho-EGFR
IC50 nM
Wild-type
LoVo cells
480
EGFR+
PC9 cells
17
Updated long-term dosing of H1975 (L858R/T790M) xenograft
with indicated doses of AZD9291
EGFR+/
T790M
H1975 cells
15
1. Cross et al. Abstract A109, AACR-EORTC-NCI conference, Boston, 2013
•
Profound regression in EGFR-mutant tumour models,
showing sustainable complete macroscopic tumour
response out to at least
200 days
Best % change from baseline in target lesions, n=34
40
30
20
D
40 D D D
40 20* 40*
D
% change from baseline in target lesion
20
10
40
0
20 80
–10
–20
–30
–40
20 20
20
20
D#
40 20
80 80 40 20
D#
40
20 80 20
20 20
40 40
80 20 80
–50
20
40
–60
20
–70
–80
T790M status
–90
Negative
Positive
Unknown
–100
D Discontinued treatment
* Imputed
# Progressive disease due to new lesion
Dose (mg/day) received noted on bar
Population: patients with observed or imputed target lesion data (n=34)
40
Best overall response‡
•
•
20
15/35 patients evaluated had a partial response (confirmed + unconfirmed)
9/18 patients with T790M+ tumours achieved a partial response (confirmed + unconfirmed)
‡Response
Evaluation Criteria in Solid Tumors v1.1, programmatically calculated from investigator-recorded tumour measurements
T790M result from local testing except for some expansion patients where local testing result unknown (central test result used)
Preliminary data, cut-off 27 September 2013
Summary of adverse events
• 89 patients have received at least one dose of
AZD9291 (data cut-off 27 September)
• No DLTs seen at dose levels of 20–160 mg/day
• There have been no dose reductions to date
• Rash and diarrhoea were mostly mild
Number of
patients without
event
Number of patients with event
Grade 1
Grade 2
Grade 3
Total
Rash
73
15
1
0
16
Diarrhoea
74
13
1
1
15
Preliminary data, cut-off 27 September 2013
Treatment
RR
(%)
PFS/TTP
(mos)
Reference
Everolimus + gefitinib or
erlotinib
0
3
Vorinostat + erlotinib
0
NR
Cetuximab + erlotinib
0
3
Dasatinib + erlotinib vs
Dasatinib
0
0
0.9
0.5
Johnson JTO ‘11
HCQ vs
HCQ + erlotinib
0
5
1.8
2
Goldberg JTO ‘12
XL647
3
3.5
Pietanza JTO ‘12
Neratinib
3
3.6
Sequist JCO ‘10
IPI-504
4
2.8
Sequist JCO ‘10
Afatinib vs
Placebo (LUX-1)
7
<1
3.3
1.1
Miller Lancet Oncol ‘12
Afatinib (LUX-4)
8
4.4
Katakami JCO ‘13
AUY922 + erlotinib
16
NR
Johnson PASCO ‘13
AUY922
20
NR
Garon PASCO ‘12
Afatinib + cetuximab
32
4.7
Janjigian ESMO ‘12
CO-1686
67
NR
Soria WCLC ‘13
AZD9291
46
NR
Ranson WCLC ‘13
Riely CCR ‘07
Regaurt PASCO ‘09
Janjigian CCR ‘11
Target
therapies
in EGFR
resistant
Response in Pts Receiving Re-Biopsy *
•
•
•
•
•
97 pts EGFR
mutati
Afatinib in linea
avanzata
RR 10.4%
PFS 3.9 mesi
OS 7.3 mesi
*22/24 evaluable pts
Pt ID
EGFR Status
baseline
EGFR Status
Before afatinib
Best response
to afatinib
2
Exon 19
Exon 18
PD
3
Exon 19
Exon 19+ T790M
PD
4
Exon 19
Exon 19 + T790M
SD
5
Exon 21
EGFR Wild type
SD
9
Exon 19
Exon 19
SD
10
Exon 19
Exon 19
PD
11
Exon 18
Exon 18
RP
15
Exon 19
Exon 19 + T790M
PD
31
Exon 21
Exon 19
PD
35
Exon 19
Exon 19 +T790M
SD
42
Exon 19
Exon 19
SD
43
Exon 19
Exon 19
PD
45
Exon 19
Exon 19
PD
47
Exon 19
Exon 19 + T790M
SD
50
Exon 19
EGFR Wild type
PD
55
Exon 19
Exon 19 + T790M
SD
67
Exon 21
Exon 21 + T790M
SD
70
Exon 19
Exon 19+T790M
PD
73
Exon 19
Exon 18
SD
79
Exon 19
Exon 18
PD
80
Exon 19
Exon 19
PD
83
Exon 19
Exon 18
SD
Cappuzzo, Tiseo, Chiari et al, Poster WCLC 2013
Nuovi farmaci alla resistenza:
considerazioni
Nuovi irreversibili potenti e molto selettivi
 Dati di risposta in caso di T790M molto promettenti
- CO-1686 67%
- AZD9291 50%
 Ridotta tossicità

“After too many trials showing too little efficacy or too much
toxicity for acquired resistance, this is a drug that has the
potential to make a major impact on this disease”
(Oxnard, Discussant AZD9291)
MO21.05: Integrated genomic analysis by whole exome and
transcriptome sequencing of tumor samples from EGFR-mutant
non-small-cell lung cancer (NSCLC) patients with acquired
resistance to erlotinib
Presenting Author: Petros Giannikopoulos, M.D.
Cancer Therapeutics Innovation Group
Co-Authors: Trever Bivona, Carlota Costa, Niki Karachaliou, John St. John, Joel Parker, Aleah F. Cauhlin, Oscar Westesson,
Nick Hahner, Urvish Parikh, Maria D. Lozano, Santiago Viteri, Jose L. Perez-Gracia, Alessandra Curioni, Eloisa Jantus-Lewintre,
Carlos Camps, Alain Vergnenegre, Radj Gervais, Anne Wellde, Jonathan Barry, George W. Wellde Jr., Andres F. Cardona, Rolf
Stahel, William R. Polkinghorn, Rafael Rosell, Jonathan Weissman
PATIENT
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
BIOPSY
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
Pre-treatment
Post-resistance
GENES HARBORING SOMATIC
MUTATIONS
EGFR T790M
Present
AMPLIFICATION
EGFR
MET
KIT, KRAS, PDGFRA, PIK3CA, SMO
Present
Present
COPY NUNUMBER ALTERED GENES
FUSION
GENES
DELETION
BRCA2, FLT3, GAS6
KRAS
MET
MYH11, RXRA
Present
EGFR, SMO, MET
EGFR
BRCA2, FLT3, FGFR1
SMO, MET
TP53, BRCA2, GAS6, RXRA, FLT3,
TP53
Present
Present
MLL
EML4-ALK
EML4-ALK
KRAS
FLT3, RXRA
MYH11
TPM3-ROS1
CTNNA2
EGFR
EGFR
SMAD4
MO21.05: Integrated genomic analysis by whole exome and transcriptome sequencing of tumor samples from EGFR-mutant non-small-cell lung cancer (NSCLC) patients with acquired resistance to erlotinib
Petros Giannikopoulos, M.D.
Conclusioni
 Nessuna
novità che impatti sulla pratica clinica
 Miglioramento delle conoscenze sulle mutazioni
EGFR uncommon
 Ancora poco chiara la migliore strategia in caso
di T790M de novo
 Risultati molto promettenti con inibitori di
EGFR irreversibili di terza generazione
 Potenziali nuovi drivers in caso di resistenza
Grazie per l’attenzione
[email protected]