-
EGFR
-
IPASS Study:Progression-free survival by EGFR mutation type (ITT
population)Post-hoc Cox analysis with covariates p-values not
calculated due to small patient numbers Exon 19 deletionL858RTime
from randomization (months)HR (95% CI) = 0.377 (0.255, 0.560) No.
events gefitinib, 46 (69.7%) No. events C/P, 65 (87.8%)Gefitinib
(n=66) Carboplatin/paclitaxel (n=74) HR (95% CI) = 0.553 (0.352,
0.868) No. events gefitinib, 48 (75.0%) No. events C/P, 40
(85.1%)
66401862074154210615604812162024GefitinibC/PPatients at risk
:643013510471720004839048121620240.00.20.40.60.81.0Probability of
progression-free survivalGefitinib (n=64) Carboplatin/paclitaxel
(n=47) MonthsMonths0.00.20.40.60.81.0Probability of
progression-free survival
-
Median OSHR n (months)(95% CI)21727.022.731.3SLOG Study:Survival
in patients with EGFR mutation+ disease1.00.80.60.40.20Probability
of PFS012243648Time (months)Median PFSHR n (months)(95%
CI)21714.011.316.71.00.80.60.40.20Probability of OS012243648Time
(months)14.027.0Rosell R, et al. N Eng J Med 2009;361:95867
- Randomized Study on Japanese Population with EGFR Mutation:
NEJGSG002Kobayashi K, et al. 2009 ASCO Abstract 8016.HR=0.357 95%
CI: 0.252-0.507, P
-
DocetaxelCisplatinGefitinibChemotherapy- nave stage IIIb/IV
NSCLC; EGFR mutation (Exon 19 or 21); PS 02; Age 18y;Progression
Free Survival R A N D O M I S E1:1Primary endpoint: PFSSecondary
endpoint: OS; ORR; QOL; SafetyWJTOG 3405Progression Free
SurvivalOverall Survival
-
EGFRDNA(10)DNA DNACTCCTC: NSCLC-74/:MALDI-MS/DNA
-
EGFR ()?EGFR?
/DNA EGFR:
-
Finding EGFR Mutation in Plasma DNA by PCR: Spanish Study
CR = complete response; PR = partial response; SD = stable
disease; PD = progressive diseaseRosell R, et al. N Eng J
Med2009;361:95867*Evaluated in the serum of 164 patientsEvaluated
in 197 patients
False Negative Rate
Response (all patients) n (%)CR24 (12.2)PR115 (58.4)CR / PR139
(70.6)SD38 (19.3)PD20 (10.2)SD / PD58 (29.4)
ValueErlotinib therapy, n (%) First-line Second- or third-line
113 (52.1) 104 (47.9)EGFR mutation, n (%) del 19 L858R 135 (62.2)
82 (37.8)EGFR mutation in serum, n (%)* del 19 L858R Not detected
64 (39.0) 33 (20.1) 67 (40.9)
-
230 pts with tumor samples for EGFR mutation analysisDHPLC
performed in plasma102 pts received gefitinib (second line)
Bai and Wang JCO 27:2653, 2009
-
DNAEGFRFalse negativeRate=18.8%False PositiveRate=20.2%=Bai and
Wang JCO 27:2653, 2009
-
IPASS: Japanese PopulationPatients recruited in Japan
(n=233)cfDNA extracted from pre-dose serum samplesDNA extracted
from paraffin-embedded archival tumor tissueEGFR mutations detected
by ARMSEGFR M+: 1/21 mutationsa (n=46)EGFR M-: 0/21 mutations
(n=148)EGFR M unknownc: (n=39)EGFR M+: 1/29 mutationsb (n=56)EGFR
M-: 0/29 mutations (n=35)EGFR M unknownc: (n=142)Comparison of
cfDNA vs tumor tissue EGFR mutations based on 22 mutations analyzed
for cfDNAand/orESMO 2009cfDNATumor tissue5 patients had a known
mutation result by tumor tissue but not cfDNA108 patients had a
known mutation result by cfDNA but not by tumor tissue86 patients
had a known mutation status by both tumor tissue and cfDNA
-
IPASS:Comparison of EGFR mutation statusin cfDNA and tumor
samplescfDNA, n EGFR M+ EGFR M- Total
2229 51
0 3535EGFR M+EGFR M-
226486TotalTumor tissue, nPatients with known cfDNA and tumor
EGFR mutation status (n=86)No false positive results Specificity
and positive predictive value 100%29/51 (56.9%) of tumor EGFR M+
were cfDNA EGFR M- (false negatives)Sensitivity 43.1% (22/51),
negative predictive value 54.7% (35/64)57/86 (66.3%)
concordanceJapanese ITT populationFalse PositiveRate=0%False
negativeRate=57.7%
- Plasma DNA as Predictive Biomarker in IPASS (Japanese
Subgroup)Treatment by subgroup interaction test, p=0.0448Japanese
ITT population; Cox analysisHR
-
/DNA EGFR
-
Wang, et al Clin.Can.Res. 2010,
-
IEGFR?
-
2009 WCLC, Okimi et al
-
,,65,(IIb)32007.8 Iressa 2009.5 Iressa21
-
IIEGFR?
-
44%EGFR-28%35.7%28.6%
-
III
-
Comparison of Somatic Gene Mutation Analysis MethodsJimeno et
al. JCO 2008
MethodPrincipleSensitivity(MT/WT;
%)TurnaroundDisadvantagesDirect SequencingNon-mutation-specific
determination of test case nucleotide sequence and comparison with
normal sequence20-50Slow turnaround (4 days to 2 weeks from
paraffin)Poorly quantitativeInsensitiveProlonged turnaroundAllele
specific probePolymerase chain reaction/selective detection10Rapid
(
-
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