Annals of Oncology

abstracts
Annals of Oncology
Astellas. K. Chi: Has received honorarium and research funding from Janssen and
Astellas. All other authors have declared no conflicts of interest.
61P
Frequency and abundance of plasma T790M mutation
associated with failure patterns of EGFR-mutant NSCLC
treated with tyrosine kinase inhibitors
60P
Circulating free tumour-derived DNA (ctDNA) to detect EGFR
mutation in patients (pts) with advanced NSCLC (aNSCLC):
French subset analysis of the ASSESS study
M.G. Denis 1 , M.P. Lafourcade 2 , G. Le Garff 3 , C. Dayen 4 , L. Falchero 5 , P. Thomas 6 ,
C. Locher 7 , G. Fraboulet 8 , G. Oliviero 9 , M. Licour 10 , N. Normanno 11 , M. Reck 12 ,
O. Molinier 13
1 Department of Biochemistry, CHU de Nantes, Nantes, France, 2 Department of
Pneumology, CH d’Angoulême, Angouleme, France, 3 Department of
Pneumology, Hopital Yves Le Foll, St. Brieuc, France, 4 Department of
Pneumology, Centre Hospitalier St. Quentin, St Quentin, France, 5 Pneumologie et
Cancérologie Thoracique, CH Villefranche-Sur-Saône, Villefranche-sur-Saône
Cedex, France, 6 Department of Pneumology, CHI Alpes du Sud - Site de Gap,
Gap, France, 7 Department of Pneumology, Centre Hospitalier Général Meaux,
Meaux, France, 8 Department of Oncology, Hopital René Dubos, Pontoise, France,
9 Department of Pneumology, CH de Longjumeau, Longjumeau, France,
10 Department of Epidemiology and Biometry, AstraZeneca, Courbevoie, France,
11 Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori – I.R.C.C.S -
Fondazione Pascale, Naples, Italy, 12 Department of Thoracic Oncology,
LungenClinic Grosshansdorf GmbH, Grosshansdorf, Germany, 13 Centre de
Coordination en Cancérologie, Centre Hospitalier Du Mans, Le Mans, France
Background: ASSESS (non-interventional diagnostic study NCT01785888) assessed
the concordance of EGFR mutation status in tumour samples and plasma ctDNA in
pts with aNSCLC in Europe and Japan. Subset data for pts from France are presented.
Methods: Pts: stage IIIA/B/IV chemo-/TKI-naïve NSCLC. Primary endpoint: EGFR
mutation status concordance between matched plasma and tumour samples. Tumour
testing was performed locally as per local practice; plasma testing was centralised.
ctDNA was extracted using the PureLink Virus Kit on an iPrep Purification Instrument
(Life Technologies) and EGFR mutations detected via the approved Therascreen EGFR
RGQ kit (Qiagen).
Results: Of 1311 enrolled pts, 145 were from France (mean age 64 years, 64% male,
83% ever-smokers). Most samples were collected from primary tumours (81%);
collection was mostly via bronchoscopy (38%) and image-guided core biopsy (19%). Of
130 pts with available tissue, 126 were evaluable for EGFR; activating mutations were
found in 13 (EGFR mutation frequency 10%). 10 pts tested positive for EGFR
mutations in plasma (EGFR mutation frequency 7%). Mutation rate was significantly
higher in never- vs ever-smokers (stepwise logistic regression: tumour p < 0.0001;
plasma p = 0.0008). Mutation status concordance could be determined for 126 (95.2%)
pts. Sensitivity of plasma testing was 61.5%. Of the 113 pts EGFR mutation-negative in
tissue, one tested plasma-positive; reanalysis via 2 different techniques confirmed the
presence of L858R, indicating a tissue false-negative result, and not a plasma
false-positive. Sensitivity was thus adjusted to 64.3% (9/14) and specificity to 100%
(112/112). One pt with a non-contributive tissue test (bone metastasis) was
plasma-positive.
Conclusions: These real-world data confirm ctDNA as a powerful alternative sample
for EGFR mutation analysis in aNSCLC.
Table: 60P Matched tissue/cytology samples (N = 126)
Unadjusted parameters n/N % Exact 95% confidence interval
Concordance 120/126 95.2 89.9, 98.2
Sensitivity 8/13 61.5 31.6, 86.1
Specificity 112/113 99.1 95.2, 100.0
Positive-predictive value 8/9 88.9 51.8, 99.7
Negative-predictive value 112/117 95.7 90.3, 98.6
Clinical trial identification: NCT01785888
Legal entity responsible for the study: AstraZeneca
Funding: AstraZeneca
Disclosure: M.G. Denis: Grants/Research support/consultant: AstraZeneca, Qiagen,
Roche Pharma, and Boehringer Ingelheim. G. Le Garff: Clin. Trial: Lilly, Roche,
AstraZeneca. All financial contributions except MUTACT study (AZ) paid by clinical
research unit. Board: Novartis. Inv. to Congress: AZ (