The APPLE Trial: Feasibility and Activity of AZD9291 (Osimertinib) Treatment on Positive PLasma T790M in EGFR-mutant NSCLC Patients. EORTC 1613.
The AZD9291 (Osimertinib) Treatment on Positive PLasma T790M in EGFR-mutant NSCLC Patients (APPLE) trial is a randomized, open-label, multicenter, 3-arm, phase II study in advanced, epidermal growth factor receptor (EGFR)-mutant and EGFR tyrosine kinase inhibitor (TKI)-naive non-small-cell lung cancer (NSCLC) patients, to evaluate the best strategy for sequencing gefitinib and osimertinib treatment. Advanced EGFR-mutant NSCLC patients, with World Health Organization performance status 0-2 who are EGFR TKI treatment-naive and eligible to receive first-line treatment with EGFR TKI will be randomized to: In all arms, a plasmatic ctDNA T790M test will be performed by a central laboratory at the Medical University of Gdansk (Poland) but will be applied as a predictive marker for making treatment decisions only in arm B. The primary objective is to evaluate the best strategy for sequencing of treatment with gefitinib and osimertinib in advanced NSCLC patients with common EGFR mutations, and to understand the value of liquid biopsy for the decision-making process. The progression-free survival rate at 18 months is the primary end point of the trial. The activity of osimertinib versus gefitinib to prevent brain metastases will be evaluated.
Department of Oncology Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Jordi
J
Remon
European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
Jessica
J
Menis
European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
Baktiar
B
Hasan
European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
Aleksandra
A
Peric
European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
Eleonora
E
De Maio
Oncology Department, University of Turin, AOU San Luigi-Orbassano, Orbassano, Italy.
Silvia
S
Novello
Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany.
Martin
M
Reck
Department of Intensive Care and Oncological Emergencies & Thoracic Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Thierry
T
Berghmans
Department of Biology and Genetics, Medical University of Gdansk, Gdańsk, Poland; Laboratory of Clinical Genetics, University Clinical Centre, Gdansk, Poland.
Bartosz
B
Wasag
European Organisation for Research and Treatment of Cancer, Brussels, Belgium; University Paris-Sud and Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: Benjamin.BESSE@gustaveroussy.fr.
Benjamin
B
Besse
Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland.
Rafal
R
Dziadziuszko
D000178:Acrylamides; D000814:Aniline Compounds; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood*; D018450:Disease Progression; D018572:Disease-Free Survival; D057915:Drug Substitution; D066246:ErbB Receptors / Q000235:genetics*; D005240:Feasibility Studies; D000077156:Gefitinib; D006801:Humans; D000073890:Liquid Biopsy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010879:Piperazines / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D012107:Research Design; D066066:Response Evaluation Criteria in Solid Tumors; D007211:Indoles; D011743:Pyrimidines
D000178:Acrylamides; D000814:Aniline Compounds; D004273:DNA, Neoplasm; D066246:ErbB Receptors; D000077156:Gefitinib; D010879:Piperazines; D011799:Quinazolines; C000596361:osimertinib; D007211:Indoles; D011743:Pyrimidines
AZD9291; Blood; EGFR mutation; Gefitinib; Lung