targeted therapies for advanced nsclc - … pathology of lung cancer...targeted therapies for...
TRANSCRIPT
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Targeted Therapies for Advanced NSCLC
Current Clinical Developments Friday, June 3, 2016
Supported by an independent educational grant from AstraZeneca
Not an official event of the 2016 ASCO Annual Meeting
Not sponsored or endorsed by ASCO or the Conquer Cancer Foundation
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Disclaimer
• This slide deck in its original and unaltered format is for educational purposes and is current as of Friday, June 3, 2016. The content and views presented in this educational activity are those of the authors/presenters and do not necessarily reflect those of Creative Educational Concepts, Inc. or the supporter.
• These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies or strategies described in this educational activity.
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Usage Rights
• This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged.
• No part of this slide deck may be published or distributed in print or electronic format without prior written permission from Creative Educational Concepts, Inc. Additional terms and conditions may apply.
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1. Review the molecular pathology of lung cancer and examine its relevance for clinical practice.
2. Outline the safety and efficacy of first-line therapies for advanced NSCLC, including first generation EGFR and ALK inhibitors.
3. Evaluate treatment approaches used to overcome EGFR and ALK resistance in advanced NSCLC, including the safety and efficacy of second- and third-line therapies and recommended molecular testing.
4. Appraise emerging concepts with EGFR TKIs and ALK inhibitors, including their role in adjuvant therapy, combination therapies, and other evolving data.
Learning Objectives
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Molecular Pathology of Lung CancerOverview and Relevance for Clinical Practice
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Pasi A. Jänne, MD, PhD Program DirectorLowe Center for Thoracic OncologyDana-Farber Cancer InstituteProfessor of MedicineHarvard Medical SchoolBoston, Massachusetts
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• Consultant for: AstraZeneca, Boehringer Ingelheim, Pfizer, Genentech, Roche, ARIAD, Chugai Pharmaceuticals, ACEA Biosciences, Merrimack Pharmaceuticals
• Research Funding: AstraZeneca, Astellas• Stockholder in: Gatekeeper Pharmaceuticals• Other: LabCorp – post-marketing royalties
from DFCI owned intellectual property on EGFR mutations
Disclosures
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EGFR
KRAS
BRAFHER2
PIK3CA
ALK
No known
genotype
ROS1NTRK1
RET
MET
EGFR
KRASKRAS
Lung AdenocarcinomaProgress in Identifying Genomic Alterations
2009
EGFR
KRAS
BRAF HER2PIK3CAALK
No known genotype
2004
2016
1984 - 2003
No known
genotype
No known
genotype
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Gandara DR, et al. Clin Cancer Res. 2015; Liao RG, et al. Lung Cancer Manag. 2012.
Lung Squamous CarcinomaGenomic Alterations
FGFR1 amplification
FGFR mutation
FGFR fusion
PIK3CAmutation/amplificationDDR2 mutation
PDGFRA amplification
BRAF mutation
EGFR amplification
ERBB2 amplification
None
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Metastatic NSCLC NCCN Guidelines Version 4.2016 SYSTEMIC THERAPY
FOR METASTATIC DISEASE
HISTOLOGIC SUBTYPE
TESTING TESTING RESULTS
Metastatic Disease
• Adenocarcinoma• Large Cell• NSCLC not
otherwise specified (NOS)
• EGFR mutation testing (category 1)
• ALK testing (category 1)
• EGFR and ALKtesting should be conducted as part of broad molecular profiling
• Consider EGFRmutation and ALKtesting especially in never smokers or small biopsy specimens, or mixed histology
• EGFR and ALK testing should be conducted as part of broad molecular profiling
See First-Line Therapy (NSCL-17)
See First-Line Therapy (NSCL-18)
See First-Line Therapy (NSCL-19)
See First-Line Therapy (NSCL-17)
See First-Line Therapy (NSCL-18)
See First-Line Therapy (NSCL-20)
• Establish histologic subtype with adequate tissue for molecular testing (consider rebiopsy if appropriate)
• Smoking cessation counseling
• Integrate palliative care(See NCCN Guidelines for Palliative Care)
Squamous cell carcinoma
Sensitizing EGFR mutation positive
ALK positive
Both sensitizing EGFR mutation and ALK are negative or unknown
Sensitizing EGFR mutation positive
ALK positive
Both sensitizing EGFR mutation and ALK are negative or unknown
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Lindeman NI, et al. J Mol Diagn. 2013.
“The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an
epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or
other clinical risk factors, and to prioritize EGFR and ALK testing over other molecular predictive tests.”
Lung Cancer CAP/IASLC/AMP Guideline
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• Availability of test?
• How quickly can you get a result?
• Do you need to test for more than one genomic alteration?
• Cost?
• Will the result help in choosing a therapy and/or enrolling a patient into a clinical trial?
Genomic Tests Factors Affecting Choice
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Gene Alteration Method LabEGFR Mutation Sequencing Molecular PathologyKRAS Mutation Sequencing Molecular PathologyALK Rearrangement FISH CytogeneticsFGFR1 Amplification FISH Cytogenetics
Genotyping can be multiplexed
FISH is difficult to multiplex
Need separate assays forALK, ROS, RET, MET, ERBB2, FGFR1
6 X $800 = $4800
Most NSCLC biopsies not amenable to 6 FISH tests & sequencing
Genomic Alterations Testing Methods
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Meyerson M, et al. Nat Rev Genet. 2010.
Next-Generation SequencingTypes of Alterations Detected
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Oncopanel DFCI/BWH Targeted NGS
Zutter MM, et al. Arch Pathol Lab Med. 2015.Neal Lindeman – Center for Advanced Molecular Diagnostics at Brigham and Woman’s Department of Pathology.
ABL1AKT1AKT2AKT3ALKALOX12BAPCAR ARAFARID1A ASXL1ATMATRXAURKAAURKBAXL B2MBAP1BCL2L12BCL6BCORBCORL1BLMBMPR1ABRAFBRCA1BRCA2
BRD4BRIP1BUB1BCARD11CBLCBLBCCND1CCND2CCND3CCNE1CD274CD58CD79BCDC73CDH1CDK1CDK2CDK4CDK5CDK6CDK9CDKN2ACDKN2BCDKN2CCEBPACHEK2CIITA
CREBBPCRKLCRLF2CRTC1CRTC2CTNNB1CUX1CYLDDDB2DDR2DICER1DIS3DMDDNMT 3AEED EGFREP 300EPHA3EPHA5EPHA7ERBB2ERBB3ERBB4ERCC2ERCC3ERCC4ERCC5
ESR1ETV1ETV4ETV5ETV6EWSR1EXT1EXT2EZH2FAM46CFAMCAFANCCFANCD2FANCEFANCFFANCGFAS FBXW7FGFR1FGFR2FGFR3FGFR4FHFKBP9FLCNFLT1FLT3
FLT4FUSGATA3GATA4GATA6GLI1GLI2GLI3GNA11GNAQGNASGPC3GSTM5H3F3AHNF1AHRASID3IDH2IGF1RIGH@IgK@IgL@IKZF1IKZF3JAK2JAK3KDM6B
KDRKITKRASLMO1MAP2K1MCL1MDM2MDM4MECOMMEF2BMEN1METMITFMLH1MLLMLL2MPLMSH2MSH6MTORMUTYHMYBMYBL1MYCMYCL1MYCNMYD88
NBNNF1NF2NFE2L2NFKBIANFKBIZFKX2-1NOTCH1NOTCH2NPM1NRASNTRK3PALB2PARK2PAX5PDCD1LG2PDGFRAPDGFRBPHF6PHOX2BPIK3C2BPIK3CAPIK3R1PIM1PMS1PMS2PNRC1
PRAMEPRDM1PRF1PRKAR1APRKCIPRKDCDPRPF40BPRPF8PSMD13PTCH1PTENPTK2PTPN11RAD21RAF1RARARB1RBL1RECQL4RELRETRFWD2RHPH2ROS1RPL26RUNX1SBDS
SDHAF2SDHBSDHCSDHDSETBP1SF1SF3B1SH2B3SMAD2SMAD4SMARCA4SMARCAB1SMC1ASMC3SMOSOCS1SOX2SRCSRSF2STAG1STAG2STAG3STK11SUFUSUZ12SUKTCF3
TERCTERTTET2TNFAIP3TP53TRA@TRB@TRG@TSC1TSC2U2AF1VHLWRNWT1XPAXPCXPO1ZNF708ZRSR2
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Molecular Testing of NSCLC DFCI Algorithm
Clinical Targeted NGS300 genes
Rearrangements in 30 genes
Advanced NSCLC Receiving therapy
Advanced NSCLC Treatment naive
Clinical Targeted NGS300 genes
Rearrangements in 30 genes
Rapid EGFRALK & ROS1 IHC
Neal Lindeman & Lynette Sholl – Center for Advanced Molecular Diagnostics at Brigham and Woman’s Department of Pathology.
Turn Around Time: 2-3 weeks
Turn Around Time: 2-3 weeks
Turn Around Time: 48-72 hours
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Molecular Testing of NSCLC NGS in The Clinic
• Targeted NGS has been adopted as our standard genotyping assay.−Results appear in medical record
• Initial experience (ASCO 2014)−Ordered on 188 pts from 7/13 – 12/13−51 (27%) insufficient−Median turnaround time was 24 days
Oxnard GR, et al. ASCO. 2014.
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Oxnard GR, et al. ASCO. 2014.
Alteration type Non-squamous (N=117) Squamous (N=17)N % N %
Point mutations EGFR 13 11% - -BRAF 6 5% 1 6%PIK3CA 6 5% 4 24%KRAS 41 35% 1 6%
Insertions/deletionsEGFR 7 6% - -HER2 2 2% - -
RearrangementsALK 4 3% - -ROS1 - - - -RET 1 1% - -
High amplificationEGFR 3 3% - -HER2 - - - -MET 4 3% - -PIK3CA 1 1% 2 12%FGFR1 1 1% - -
NSCLC Spectrum of Genomic Alterations
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Oxnard GR, et al. ASCO. 2014.
NGS in The Clinic It Can Help Guide Clinical Management
61 yo never smoker; s/p 1st line chemotherapy; tumor pan “wild type” by conventional genomic assays
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Oxnard GR, et al. ASCO. 2014.
NGS in The Clinic It Can Help Guide Clinical Management
61 yo never smoker; s/p 1st line chemotherapy; tumor pan “wild type” by conventional genomic assays
Baseline After 3 months
• Patient initiated second-line erlotinib at 150 mg daily and had a response in lung mass
• Developed progression in brain after 5 months, but systemic response has been sustained now 9 months on erlotinib
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EGFR
KRAS
BRAFHER2
PIK3CA
ALK
No known
genotype
ROS1NTRK1
RET
MET
EGFR
KRASKRAS
Lung AdenocarcinomaProgress in Identifying Genomic Alterations
2009
EGFR
KRAS
BRAF HER2PIK3CAALK
No known genotype
2004
2016
1984 - 2003
No known
genotype
No known
genotype
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Shaw AT, et al. N Engl J Med. 2014; Mazières J, et al. J Clin Oncol. 2015.
Crizotinib in ROS1-rearranged NSCLC Efficacy
Disease progressionStable diseasePartial responseComplete response
100
80
60
40
20
0
-20
-40
-60
-80
-100
Chan
ge fr
om b
asel
ine
(%)
* M A
RR: 72%; PFS: 19.2 months
120
10080
60
40
200
-20
-40
-60
-80
-100
-120
Chan
ge (%
)
93100
28
0 0
-30 -30-40 -40-40-40-44-45-50
-52-55-59
-65-66-69-70-75-80
-90-100-100 -100-100
-100
No. of previous lines of
chemotherapy before
crizotinib
5 3 4 4 5 1 1 1 1 4 6 3 4 1 1 5 4 3 9 2 1 4 2 5 0 1 1 2 2
RR: 80%; PFS: 9.1 months
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Paik, et al. J Clin Oncol. 2011; Marchetti, et al. J Clin Oncol. 2011; Cardarella, et al. Clin Cancer Res. 2013.
NSCLC Summary of BRAF Mutations
Author N Histology Stage TestingPaik 697 ADC I-IV V600, D594, G469
Marchetti 1046 ADC & SCC I-IV Exons 11 & 15
Cardarella 883 ADC I-IV Exons 11 & 15
Exon 11 Ex 12 Ex 13 Ex 14 Exon 15
V600E
V600L, K601 E/N, T599_V600InsT, V600E_K601delInsE
W604R, G606 A/VL597 R/V/Q
D594 G/N
G469AG464 E/V
G469delG466 V/R
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Frequency of BRAF MutationsMelanoma vs Lung Adenocarcinoma
V600E
Non-V600E
V600ENon-
V600E
Melanoma Lung Adenocarcinoma
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Davies H, et al. Nature. 2002; Platz A, et al. Mol Oncol. 2008; Karasarides M, et al. Oncogene. 2004; Long, et al. N Engl J Med. 2014; Gilmartin, et al. Clin Cancer Res. 2011.
Inhibiting MAPK/ERK PathwayDabrafenib and Trametinib
Dabrafenib mode of action• Reversible, small molecule • BRAF inhibitor • ATP competitive• BRAF V600E: IC50 0.65 nM
Trametinib mode of action• Reversible, small molecule • MEK1 and MEK2 allosteric
inhibitor • MEK1 and MEK2: IC50 0.7
and 0.9 nM
PI3K/AKT/mTORpathway
Proliferation, Growth, Survival
MEK
p90RSK MSK1
BRAF CRAF
BRAFV600
ERK1/2
RAS
DabrafenibTrametinib
RTKs SOSGrb2SHCPPPP
PP
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Planchard D, et al. Lancet Oncol. 2016.
BRAF V600E NSCLCDabrafenib Monotherapy
Max
imum
Per
cent
Red
uctio
n fr
om B
asel
ine
Mea
sure
men
t
SDPDNE
PRBest Confirmed Response
380
360
340
100
80
60
40
20
0
-20
-40
-60
-80
-100
RR: 33%PFS: 5.5 months
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Planchard D, et al. ASCO. 2015.
BRAF V600E Metastatic NSCLCDabrafenib + Trametinib
Max
imum
Per
cent
Red
uctio
n at
Tim
e of
Bes
t D
isea
se A
sses
smen
t
20
10
0
-10
-20
-30
-40
-50
-60
-70
-80
-90
-100
Best Confirmed ResponsePRSDPD
One patient discontinued at day 23 and did not have any post-baseline scans for efficacy.
RR: 63%PFS: Not Reached
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Break
32,316,377 bp
KIF5BATG ATG
RET Break
43,611,118 bp
ATGATG
KIF5B-RETRET-KIF5B
RET-KIF5B Translation
Cadherin
Not expressedKIF5B (exons 16-25) RET (exons 1-11)
TranslationKIF5B-RET
Kinesin Coiled coil Tyrosine kinaseKIF5B (exons 1-15) RET (exons 12-20)
Expressed
Lung AdenocarcinomaALK and RET Gene Fusions
Several drugs (sunitinib, sorafenib, vandetanib, cabozantinib) inhibit RET but none are specific RET inhibitors
Lipson D, et al. Nat Med. 2012.
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Best Response % (N)
PR 44% (7/16)
Confirmed 38% (6/16)
Unconfirmed 6% (1/16)
SD 56% (9/16)
ORR 38% (95% Cl 15%-65%)
ORR12wks 36% (95% Cl 13%-65%)(5 PRs of 14 evaluable at 12 wks)
30%
0%
-30%
-60%
-90%
Confirmed PRSD
RET-Rearranged Lung AdenocarcinomaResponse to Cabozantinib
Drilon AE, et al. ASCO. 2015.
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Awad MM, et al. J Clin Oncol. 2016.
NSCLCMET Exon 14 Skip Mutations
MET exon 14 cancers can have METamplification and/or high level of MET
expression
KRAS (34%)
No oncogenic mutation
identified (30%)
EGFR (19%)
ALK (3.9%)
BRAF (3.8%)
MET ex14 (3%)
PIK3CA (2.9%)
ERBB2 (2.5%)
NRAS (1%)
RET (1%)
ROS1 (1%)AKT (<1%)
HRAS (<1%)
MAP2K1 (<1%)
Prevalence of MET exon 14 skip mutations
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Awad MM, et al. J Clin Oncol. 2016.
MET Exon 14 Skip TumorsSensitive to MET Inhibitors
Pre-Treatment On Crizotinib (at 2 months)
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NSCLC With Genetic Alterations Emerging Targeted Agents
Clinical Practice Guidelines. NCCN. 2016.V4.
Genetic Alteration (eg, driver event)Available Targeted Agents with Activity Against Driver Event in
Lung CancerBRAF V600E mutation* vemurafenib
dabrafenibdabrafenib + trametinib
High level MET amplification or MET exon 14 skipping mutation
crizotinib
RET rearrangements cabozantinibROS1 rearrangements crizotinibHER2 mutations trastuzumab (category 2B)
afatinib (category 2B)*Non-V600E mutations have variable kinase activity and response to these agents
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Do Genomic Changes Predict for Sensitivity to Immunotherapy?
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Mutation Load Across Cancer TypesHigh Mutational Burden in Lung Cancer
Alexandrov LB. Nature. 2013.
1000/Mb
100/Mb
10/Mb
1/Mb
0.1/Mb
0.01/Mb
n= 2 20 133
26 23 53 114
227
14579180 63 11 216
384
213
51 20 231
186
178
6944 274
7349 96
Som
atic
mut
atio
n ra
te
Rhab
doid
LAM
Ewin
g
AML
Med
ullo
Carc
inoi
d
Thyr
oid
NB
CLL
LGG
Brea
st
Pros
tate
Panc
reas
MM
Kidn
eyRP
Kidn
eyRC OV
GBM
Ute
rine
Cerv
ical
CRC
Head
Nec
k
DLBC
L
Stom
ach
Esop
h
Blad
der
LUAD
LUSC
Mel
anom
a
C > TC > AC > GT > CT > AT > G
20
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Anti-PD-1/PD-L1 mAbs in NSCLCImpact of Smoking Status
AgentORR, % (n/N)
Current/former smoker Never smoker
Pembrolizumab1,2 26%(NR/129)
8%(NR/60)
Atezolizumab3,4 26%(11/43)
10%(1/10)
AgentORR, % (n/N)
>5 pack-years ≤5 pack-years
Nivolumab5 37%(19/52)
0%(0/10)
1Garon E, et al. WCLC. 2013. (Abstract MO18.02); 2Garon E, et al. ASCO. 2014. (Abstract 8020); 3Horn L, et al. WCLC. 2013. (Abstract 2347); 4Soria J, et al. ECC. 2013. (Abstract 3408); 5Hellmann MD, et al. ESMO. 2014. (Abstract 1229PD)
NR=not reported
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DCB NDB
All Tumors
# N
onsy
nony
mou
s m
utat
ions
/tum
or
1200
800
400
200
0
# N
onsy
nony
mou
s m
utat
ions
/tum
or
1200
800
400
200
0
Validation Cohort
DCB NDB
800
600
400
200
0
# N
onsy
nony
mou
s m
utat
ions
/tum
or
DCB NDB
Discovery Cohort100
50
0
% S
ensi
tivity
1 - % Specificity50 100
High nonsynonymous burdenLow nonsynonymous burden
High nonsynonymous burdenLow nonsynonymous burden
Perc
ent p
rogr
essi
on-fr
ee
Perc
ent p
rogr
essi
on-fr
eeMonths Months
Validation Cohort All Tumors
100
50
0
100
50
0
4 8 12 16 20 244 8 12 16 20 24 4 8 12 16 20 24
High nonsynonymous burdenLow nonsynonymous burden
Perc
ent p
rogr
essi
on-fr
ee
Months
Discovery Cohort
100
50
0
Clinical Benefit of Anti-PD-1 TherapyEffect of Nonsynonymous Mutation Burden
Rizvi NA, et al. Science. 2015.
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Clinical Benefit of Anti-PD-1 TherapyEffect of Molecular Smoking Signature
Rizvi NA, et al. Science. 2015.
(n=18) (HR 0.15, 95% 0.06-0.39, log-rank P=.0001)
100
Months
Perc
ent p
rogr
essi
on-fr
ee
50
04 8 12 16 20 24
Transversion highTransversion low
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Anti-PD-1/PD-L1 mAbs in NSCLCImpact of EGFR, KRAS Status
AgentORR, % (n/N)
Mutant Wild-type Unknown
Nivolumab1 17% (2/12) 20% (11/56) 15% (9/61)Atezolizumab2,3 17% (1/6) 23% (9/40) NR
1Gettinger SN, et al. J Clin Oncol. 2015; 2Horn L, et al. WCLC. 2013. (Abstract 2347); 3Soria J, et al. ECC. 2013. (Abstract 3408)
EGFR Status
KRAS Status
AgentORR, % (n/N)
Mutant Wild-type Unknown
Nivolumab1 14% (3/21) 25% (9/36) 14% (10/72)Atezolizumab2 10% (1/10) 30% (8/27) NR
NR=not reported
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Clinical Benefit of Anti-PD-1 TherapyOS in Predefined Subgroups
Borghaei H, et al. N Engl J Med. 2015.
Nivolumab Better
Docetaxel Better
0.25 0.5 1 2 4
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Noninvasive Detection of Response and Resistance
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Liquid BiopsyCirculating Tumor-Derived Cells or DNA
Crowley E, et al. Nat Rev Clin Oncol. 2013.
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Plasma ddPCRDetection of Mutations in ctDNA
Oxnard GR, et al. Clin Cancer Res. 2014.
EGFR L858R KRAS G12C100
80
60
40
20
0
0 20 40 60 80 100
AUC=0.86 (0.71-1.01)
False positive rate (%)
Sens
itivi
ty (%
)
100
80
60
40
20
0
0 20 40 60 80 100
AUC=0.9 (0.76-1.04)
False positive rate (%)
Sens
itivi
ty (%
)
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Plasma ddPCRNon-Invasive Disease Monitoring
Oxnard GR, et al. Clin Cancer Res. 2014.
Serial monitoring for EGFR activating and EGFR T790M resistance mutation in erlotinib treated EGFR mutant patients
Stage IV NSCLCEGFR mutant
Treatment naive
Erlotinib
150 mg
Biopsy at resistanceCirculating tumor cells
Plasma for ctDNA
5000
1000
100
10
0 8 16 24 32 40 48 56 64N/D
PD
Weeks on treatmentEG
FR m
utat
ion
Conc
entr
atio
n/
100µ
L of
DN
A
5000
1000
100
10
0 8 16 24 32 40 48 56 64N/D
PD
Weeks on treatment
EGFR
mut
atio
n Co
ncen
trat
ion
/ µL
of D
NA
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Prospective ValidationDFCI# 14-147 Schema
Cohort 3: Genotyped patients starting new treatment
*(Only patients with a detectable plasma
genotype who are starting a new systemic therapy)
Follow until progression (advanced
pts)
Diagnostic analysis Follow-up analysis*Enrollment
Compare plasma &
tumor genotype
2 bloodspecimens on therapy
Collect 2 pairedblood
specimens
Cohort 1: First-line patients
Cohort 2: Acquired resistance patients
Same day registration and initial blood draw
Adrian Sacher, Geoff Oxnard, Cloud Paweletz
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Detection of EGFR and KRAS MutationsValidation of Plasma Genotyping
Sacher AG, et al. JAMA Oncol. 2016.
100%
80%
60%
40%
20%
Assa
y se
nsiti
vity
Number of metastatic sites
01 2 3 >4
100000
10000
1000
100
10
N/D
Mut
atio
n co
ncen
trat
ion/
mL
of
plas
ma
Tissue Genotype
EGFR exon19 del assay
EGFRL858Rassay
EGFRT790Massay
KRASG12Xassay
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Plasma ddPCR Advantages
Sacher AG, et al. JAMA Oncol. 2016.
Day 0: Plasma ddPCR
ordered
Day 0: Repeat biopsy
ordered
Day 1: EGFR
T790M plasma positive
Day 25: EGFR
T790M tissue
positive
Day 31: osimertinib
initiated
24 day delay in initiating therapy while awaiting
tissue genotyping
Symptomatic disease progression
on erlotinib
Clinical and radiographic
response to AZD9291
• Plasma ddPCR detected EGFR and KRAS mutations rapidly with the high specificity needed to select therapy and avoid repeat biopsies.
• Plasma ddPCR may also detect EGFR T790M missed by tissue genotyping due to tumor heterogeneity in resistant disease.
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Plasma NGS Detects Actionable Genomic Alterations
MET
copy
num
ber
EGFR T790M
RET
EGFR C797S
KIF5
EGFR KELREATSPK>KENSPK
Paweletz CP, et al. Clin Cancer Res. 2016.
RET Rearrangement MET amplification
EGFR TKI resistance Novel EGFR mutation
522511Sample
18 105
3.5
3.0
2.5
1.5
2.0
KIF5
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Molecular Pathology of Lung Cancer Summary
• Genomic testing can identify targetable drug sensitive alteration.
• Multiplex genomic testing should be standard of care.− Identify both common and rare but targetable
alterations−May help select patients more likely to benefit
from immunotherapy• Blood testing is rapidly evolving and will
complement and/or augment tissue based testing.
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