35O_PR - Investigating the utility of circulating-free tumour-derived DNA (ctDNA) in plasma for the detection of epidermal growth factor receptor (EGFR) muta...

Date 17 April 2015
Event ELCC 2015
Session ESMO-IASLC Best Abstracts
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Martin Reck
Citation Annals of Oncology (2015) 0 (0): 1-8. 10.1093/annonc/mdv128
Authors M. Reck1, K. Hagiwara2, B. Han3, S. Tjulandin4, C. Grohe5, T. Yokoi6, A. Morabito7, R. McCormack8, M. Ratcliffe8, N. Normanno9
  • 1Department Of Thoracic Oncology, LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Centre for Lung Research (DZL), 22927 - Grosshansdorf/DE
  • 2Department Of Respiratory Medicine, Saitama Medical University, Iruma-gun/JP
  • 3Department Of Respiratory Medicine, Shanghai Chest Hospital, Jiao Tong University, Shanghai/CN
  • 4Department Of Clinical Pharmacology And Chemotherapy, Russian Cancer Research Center, Moscow/RU
  • 5Arzt Fur Innere Medizin, Pneumologie Und Kardiologie, Evangelische Lungenklinik, Berlin/DE
  • 6The Department Of Thoracic Oncology, Kansai Medical University Hirakata Hospital, Osaka/JP
  • 7Thoraco-pulmonary Medical Oncology, Instituto Nazionale Tumori Fondazione Pascale, Naples/IT
  • 8Personalized Healthcare And Biomarkers, AstraZeneca, Macclesfield/UK
  • 9Cell Biology And Biotherapy Unit, Instituto Nazionale Tumori Fondazione Pascale, Naples/IT



ASSESS (a large multicentre non-interventional diagnostic study; NCT01785888) evaluated EGFR mutation status concordance between plasma-derived ctDNA vs tissue (as per local testing) in pts with aNSCLC.

EGFR mutation frequency, n/N (%) First-line treatment choice (most common only; tissue/cytology), n/N (%)
Tissue/cytology Plasma EGFR mutation-positive EGFR mutation-negative
Overall 191/1184 (16) 191/1263 (9) Gefitinib 97/191 (51) Pemetrexed 423/993 (43) Carboplatin 339/993 (34)
Europe 105/903 (12) 82/972 (8) Gefitinib 42/105 (40) Pemetrexed 358/798 (45) Carboplatin 264/798 (33)
Japan 86/281 (31) 37/291 (13) Gefitinib 55/86 (64) Carboplatin 75/195 (38) Pemetrexed 65/195 (33)
ADC 177/907 (20) 109/952 (11)
Non-ADC 12/257 (5) 9/288 (3)
Mutation subtype
Exon 19 deletions 94/191 (49) 68/119 (57)
L858R 65/191 (34) 38/119 (32)
Correlations between demographic/disease status factors and EGFR mutation status
Demographic/disease status factor Tissue/cytology Plasma
% p-value OR 95% CI % p-value OR 95% CI
ADC vs non-ADC 20 vs 5 0.0001 4.020 1.994-8.107 11 vs 3 0.0075 3.005 1.342-6.731
Never - vs ever-smoker 46 vs 8 <0.0001 6.182 4.035-9.473 27 vs 5 <0.0001 4.407 2.746-7.071
Female vs male 29 vs 10 0.0028 1.903 1.248-2.902 18 vs 5 0.0048 1.976 1.232-3.170
Japanese vs European 31 vs 12 <0.0001 5.159 3.394-7.841 13 vs 8 0.0905 1.520 0.936-2.469
Greater number of organs with metastases, % of patients with EGFR mutation-positive NSCLC with 1/2/3/ ≥ 4 metastatic organs N/A N/A N/A N/A 9/10/17/15 0.0540 1.202 0.997-1.450

OR, odds ratio; N/A, not available


Eligible pts had newly diagnosed local/metastatic (stage IIIA/B/IV) chemotherapy- and EGFR tyrosine kinase inhibitor-naïve aNSCLC. Primary endpoint: EGFR mutation status concordance between matched plasma and tissue/cytology samples. Secondary endpoints: EGFR mutation frequency by histology; correlation between mutation status and demographic/disease status; EGFR testing practices; treatment decisions.


1311 pts were enrolled from 56 centres in Europe/Japan; 1288 (291 Japan) eligible. Mutation status concordance in 1162 matched samples was 89% (95% CI 87–91); pooled test sensitivity for plasma tests: 46% (39–53); specificity 97% (96–98); positive predictive value (PPV) 78% (69–85); negative predictive value 90% (88–92). PPV was 93% in pts whose plasma and tumour were tested with identical highly sensitive methods. In a subset of 94 Japanese pts, initial sensitivity was only 17% but increased to 52% when plasma was retested using an optimised ctDNA extraction method. Mutation frequency was significantly higher in: adenocarcinoma (ADC) vs non-ADC (40% vs 8% Japan, 14% vs 3% Europe), never-smokers, women, Japanese pts, and with increasing number of metastatic organs (plasma samples only; Table). Median mutation test turnaround: 10 days.


These first real-world data suggest ctDNA is a feasible suitable sample for EGFR mutation analysis when tumour samples are unavailable; robust/sensitive analysis methods should be used to reduce false negative results in both plasma and tumour.


M. Reck: Speakers bureau: Hoffmann-La Roche, Lilly, BMS, AstraZeneca, Pfizer, Daiichi-Sankyo, Boehringer Ingelheim; Consultant: Hoffmann-La Roche, Lilly, BMS, AstraZeneca, Pfizer, Daiichi-Sankyo, Boehringer Ingelheim, MSD.

K. Hagiwara: Speakers bureau: AstraZeneca, Pfizer, Chugai Pharmaceuticals; Patent: LSI Medience.

B. Han: Speakers bureau: Roche, AstraZeneca; Consultant: AstraZeneca, Pfizer.

S. Tjulandin: Speakers bureau: AstraZeneca Grants/research support: Celgene.

C. Grohe: Speakers bureau: Roche, AstraZeneca; Consultant: AstraZeneca, Pfizer, Roche.

A. Morabito: Speakers bureau: AstraZeneca, Roche, Boehringer Ingelheim; Consultant: Pfizer, Daiichi-Sankyo.

R. McCormack and M. Ratcliffe: Employee of AstraZeneca and hold shares in AstraZeneca.

N. Normanno: Grants/research support/consultant: AstraZeneca.

All other authors have declared no conflicts of interest.

Clinical trial identification

This study is available on clinicaltrials.gov (NCT01785888) with a first received date of February 4th 2013. No study results have yet been posted.