Annals of Oncology
Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses:
Legal entity responsible for the study: F. Hoffmann-La Roche, Ltd.
Funding: F. Hoffmann-La Roche, Ltd.
Disclosure: A. Ardizzoni: Honoraria (self): Eli-Lilly; Honoraria (self): Pfizer; Honoraria (self),
Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: MSD;
Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy:
AstraZeneca; Research grant / Funding (institution): Celgene. S. Azevedo: Honoraria (self), Advisory /
Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche;
Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS;
Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses:
Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene;
Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Research grant /
Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy:
MSD. D. Rodriguez Abreu: Full / Part-time employment: Insular University Hospital in Gran
Canaria, Spain; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb;
Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory /
Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau /
Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory
/ Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau /
Expert testimony: AstraZeneca. J. Alatorre-Alexander: Advisory / Consultancy, Speaker Bureau /
Expert testimony, Travel / Accommodation / Expenses: Merck-Sharp & Domme; Advisory /
Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca;
Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses:
Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation /
Expenses: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel /
Accommodation / Expenses: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony,
Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testi-
mony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert
testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Leadership role: Head of
Oncology in National Institute of Respiratory Diseases Mexico ; Full / Part-time employment:
Medical oncologist National Institute of Respiratory Diseases. H.J. Smit: Advisory / Consultancy:
MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Leadership role: Secretary
section oncology NVALT (Dutch lung phycisions organasation); Leadership role: president DLCA
(Dutch Lung Cancer Audit). K. Syrigos: Speaker Bureau / Expert testimony: MSD; Research grant /
Funding (institution): ROCHE; Research grant / Funding (institution): NOVARTIS; Research grant /
Funding (institution), Travel / Accommodation / Expenses: BMS; Travel / Accommodation /
Expenses: GENESIS. H. Patel: Full / Part-time employment: Genentech/Roche. J. Tolson: Full / Part-
time employment: Roche. A. Cardona: Honoraria (institution), Full / Part-time employment: F.
Hoffmann-La Roche . P. Perez Moreno: Full / Part-time employment: Roche/Genentech. T. Newsom-
Davis: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel /
Accommodation / Expenses: AstraZenca,; Honoraria (self), Advisory / Consultancy, Speaker Bureau /
Expert testimony, Travel / Accommodation / Expenses: BMS,; Honoraria (self), Advisory /
Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer
Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel /
Accommodation / Expenses: Eli Lilly,; Honoraria (self), Advisory / Consultancy, Speaker Bureau /
Expert testimony, Travel / Accommodation / Expenses: MSD,; Honoraria (self), Advisory /
Consultancy, Travel / Accommodation / Expenses: Otsuka,; Honoraria (self), Advisory / Consultancy,
Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche,; Honoraria (self),
Volume 30 | Supplement 5 | October 2019
abstracts
Takeda; Advisory / Consultancy: Amgen,; Advisory / Consultancy: Pfizer,; Leadership role: Vice-
Chair, British Thoracic Oncology Group. All other authors have declared no conflicts of interest.
LBA85 Longitudinal circulating tumour DNA (ctDNA) monitoring for early
detection of disease progression and resistance in advanced NSCLC
in FLAURA
J.E. Gray1, N. Peled2, A. Markovets3, N. Nogami4, J-S. Lee5, B.C. Cho6,
B. Chewaskulyong7, M. Majem8, T. Reungwetwattana9, K. Vishwanathan10, A. Todd11,
Y. Rukazenkov12, M. Johnson13, C. Barrett3, J. Chmielecki3, R. Hartmaier3,
S.S. Ramalingam14
1
Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute,
Tampa, FL, USA, 2Medical Oncology, Soroka Medical Center & Ben-Gurion University,
Beer-Sheva, Israel, 3Translational Medicines, Research and Early Development,
Oncology R&D, AstraZeneca, Boston, MA, USA, 4Department of Thoracic Oncology,
National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan, 5Medical
Oncology, Seoul National University Bundang Hospital, Seoul, Republic of Korea,
6
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center,
Yonsei University College of Medicine, Seoul, Republic of Korea, 7Oncology Unit,
Department of Medicine, Chiang Mai University, Chiang Mai, Thailand, 8Department of
Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 9Division of
Medical Oncology, Department of Medicine, Faculty of Medicine, Ramathibodi
Hospital, Mahidol University, Bangkok, Thailand, 10Clinical Pharmacology and Safety
Science, R&D, AstraZeneca, Boston, MA, USA, 11Oncology Biometrics, Oncology R&D,
AstraZeneca, Cambridge, UK, 12Oncology R&D, AstraZeneca, Cambridge, UK,
13
Quantitative Clinical Pharmacology, Research and Early Development, Oncology
R&D, AstraZeneca, Cambridge, UK, 14Department of Hematology and Medical
Oncology, Emory University, Winship Cancer Institute, Atlanta, GA, USA
Background: In the phase III FLAURA study (NCT02296125), the 3rd-generation
EGFR-TKI osimertinib showed superior efficacy to comparator EGFR-TKIs in previ-
ously untreated EGFR-mutated (EGFRm) advanced non-small cell lung cancer
(NSCLC). Here we report results from an exploratory analysis of ctDNA for the early
detection of disease progression (PD) in FLAURA.
Methods: Treatment-naı̈ve patients (pts) with EGFRm (ex19del/L858R) locally
advanced/metastatic NSCLC (n ¼ 556) were randomised 1:1 (osimertinib 80 mg qd:
comparator [gefitinib 250 mg qd/erlotinib 150 mg qd]). Plasma samples were collected
on Days 1, 8 and 15, then every 21 days for weeks (W) 3–18, then every 6W thereafter.
In pts who had a plasma sample on PD and/or discontinuation, ctDNA droplet digital
PCR (ddPCR; Biodesix) for EGFRm (ex19del/L858R/T790M) was performed at all
available time points and C797S for post-W6 time points. C797S and T790M were the
only resistance mutations assayed. ctDNA progression was defined with respect to the
nadir ctDNA result and its proximity to the ddPCR detection and quantification limits.
Results: The ctDNA progression analysis included 122/556 (22%) pts with valid longi-
tudinal monitoring ddPCR data and RECIST PD by DCO1 (12 June 2017). Across both
arms, ctDNA progression preceded or co-occurred with PD in 80/122 (66%) pts with
2.7 months (mo) median lead time; 9.5 mo median progression-free survival (mPFS;
n ¼ 80). Acquired C797S or T790M was detected in 57/122 (47%) pts with ctDNA pro-
gression (osimertinib 4/50 [8%] C797S, comparator 53/72 [74%] T790M); median
time to detection was 16.7 and 8.4 mo for the osimertinib and comparator arms,
respectively, mirroring overall mPFS. In pts with ctDNA progression and PD
(n ¼ 106), acquired T790M and C797S were detected either at the same time as, or ear-
lier than PD in 41/106 (38%) pts (osimertinib 2/39 [5%], comparator 39/67 [58%]);
median lead time was 1.4 mo.
Conclusions: ctDNA monitoring may allow for earlier identification of pts who prog-
ress on first-line EGFR-TKI therapy and the detection of EGFR-mediated resistance
mechanisms in advance of PD in EGFRm NSCLC. Future work aims to explore early
detection of non-EGFR-mediated resistance.
Clinical trial identification: NCT02296125.
Editorial acknowledgement: Writing support was provided by Donna Tillotson, PhD
of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc,
and funded by AstraZeneca.
Legal entity responsible for the study: AstraZeneca.
Funding: AstraZeneca.
Disclosure: J.E. Gray: Research grant / Funding (institution): Array; Research grant / Funding (insti-
tution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution):
AstraZeneca; Research grant / Funding (institution): Genentech; Research grant / Funding (institu-
tion): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding
(institution): Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Honoraria (self), Advisory /
Consultancy: Takeda. N. Peled: Honoraria (self), Advisory / Consultancy, Research grant / Funding
(self): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self):
Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self):
Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self):
MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria
(self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory /
Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy,
Research grant / Funding (self): Takeda; Advisory / Consultancy: Eli Lilly; Honoraria (self):
Foundation Medicine; Shareholder / Stockholder / Stock options: NovellusDx; Honoraria (self):
Gaurdant360. A. Markovets: Shareholder / Stockholder / Stock options, Full / Part-time employment:
AstraZeneca. N. Nogami: Honoraria (self): Pfizer Inc.; Honoraria (self): Chugai Pharmaceutical Co.
Ltd; Honoraria (self): Eli Lilly; Honoraria (self): Taiho Pharmaceutical Co. Ltd; Honoraria (self):
AstraZeneca; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Ono Pharmaceutical Co. Ltd;
doi:10.1093/annonc/mdz394 | v921
abstracts
Honoraria (self): BMS; Honoraria (self): MSD. B.C. Cho: Honoraria (institution), Advisory /
Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis;
Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bayer;
Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution):
AstraZeneca; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution):
MOGAM Institute; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (insti-
tution): Dong-A ST; Honoraria (institution), Advisory / Consultancy, Research grant / Funding
(institution), Licensing / Royalties: Champions Oncology; Honoraria (institution), Advisory /
Consultancy, Research grant / Funding (institution): Janssen; Honoraria (institution), Advisory /
Consultancy, Research grant / Funding (institution): Yuhan; Honoraria (institution), Advisory /
Consultancy, Research grant / Funding (institution): Ono; Honoraria (institution), Advisory /
Consultancy, Research grant / Funding (institution): Dizal Pharma; Honoraria (institution), Advisory
/ Consultancy, Research grant / Funding (institution): MSD; Honoraria (institution), Advisory /
Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory / Consultancy: Roche;
Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory /
Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Eli Lilly; Honoraria (institu-
tion), Advisory / Consultancy: Takeda; Shareholder / Stockholder / Stock options: TheraCanVac Inc.
B. Chewaskulyong: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony,
Research grant / Funding (institution): AstraZeneca. M. Majem: Advisory / Consultancy, Speaker
Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony, Research grant / Funding
(self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert
testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau /
v922 | NSCLC, metastatic
Annals of Oncology
Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker
Bureau / Expert testimony: Boehringer; Advisory / Consultancy: Tesaro; Speaker Bureau / Expert testi-
mony: Hellsin; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: Takeda; Advisory /
Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony:
Amgen. K. Vishwanathan: Shareholder / Stockholder / Stock options, Full / Part-time employment:
AstraZeneca. A. Todd: Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder /
Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Johnson: Shareholder /
Stockholder / Stock options, Full / Part-time employment: AstraZeneca. C. Barrett: Shareholder /
Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Chmielecki: Shareholder /
Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Hartmaier: Shareholder /
Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Shareholder / Stockholder /
Stock options, Licensing / Royalties, Nfe2l2 exon 2 ano/or exon 3 loss from work conducted at
Foundation Medicine; provisional patent filed: Foundation Medicine. S.S. Ramalingam: Honoraria
(self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self),
Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory /
Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy,
Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy: Roche/
Genentech; Honoraria (self), Advisory / Consultancy: Loxo; Honoraria (self), Advisory / Consultancy:
Nektar; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Tesaro;
Research grant / Funding (institution): Advaxis; Research grant / Funding (institution): Takeda. All
other authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | October 2019