TY - JOUR
TI - A Real-World, Observational, Prospective Study to Assess the Molecular
Epidemiology of Epidermal Growth Factor Receptor (EGFR) Mutations upon
Progression on or after First-Line Therapy with a First- or
Second-Generation EGFR Tyrosine Kinase Inhibitor in EGFR
Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung
Cancer: The `LUNGFUL' Study
AU - Mountzios, Giannis
AU - Koumarianou, Anna
AU - Bokas, Alexandros and
AU - Mavroudis, Dimitrios
AU - Samantas, Epaminondas
AU - Fergadis, Evangelos
AU - Georgios
AU - Linardou, Helena
AU - Katsaounis, Panagiotis and
AU - Athanasiadis, Elias
AU - Karamouzis, V, Michalis
AU - Pentheroudakis,
AU - George
AU - Lampaki, Sofia
AU - Froudarakis, Marios E.
AU - Perdikouri,
AU - Eleni-Isidora A.
AU - Somarakis, Alvertos
AU - Papageorgiou, Foteini and
AU - Paparepa, Zoe
AU - Nikolaou, Aristeidis
AU - Syrigos, Konstantinos N.
JO - Blood cancer journal
PY - 2021
VL - 13
TODO - 13
SP - null
PB - MDPI
SN - null
TODO - 10.3390/cancers13133172
TODO - biopsy; carcinoma; non-small-cell lung cancer; EGFR-tyrosine kinase
inhibitor; epidermal growth factor receptor; T790M mutation
TODO - Simple Summary Non-small cell lung cancer (NSCLC) accounts for
approximately 85% of lung cancer cases, with few patients carrying
driver mutations in the gene encoding for epidermal growth factor
receptor (EGFR). Advances in translational research have established
EGFR tyrosine kinase inhibitors (TKIs) as the standard first-line
therapy for NSCLC patients with activating EGFR mutations. The aim of
our observational study was to assess the frequency of T790M acquired
resistance and predictors of its presence, in patients with EGFR-mutated
locally advanced or metastatic NSCLC who have progressed in the
first-line EGFR-TKI treatment setting with first- or second-generation
TKIs and have undergone molecular testing in tissue and/or plasma
biopsy. The study highlights the challenges of performing tissue
re-biopsy in routine care settings, which can lead to patients
considered non-eligible for certain therapies from which they can
benefit, and merits further actions from the healthcare community, in
order to establish re-biopsy as a standard procedure. Background:
Real-world data on the molecular epidemiology of EGFR resistance
mutations at or after progression with first- or second-generation
EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This
ongoing observational study was carried out by 23 hospital-based
physicians in Greece. The decision to perform cobas EGFR Mutation Test
v2 in tissue and/or plasma at disease progression was made before
enrollment. For patients with negative/inconclusive T790M plasma-based
results, tissue re-biopsy could be performed. Results: Ninety-six (96)
eligible patients were consecutively enrolled (median age: 67.8 years)
between July-2017 and September-2019. Of the patients, 98% were tested
upon progression using plasma and 2% using tissue/cytology biopsy. The
T790M mutation was detected in 16.0% of liquid biopsies. Tissue
re-biopsy was performed in 22.8% of patients with a T790M-negative
plasma result. In total, the T790M positivity rate was 21.9%, not
differing between patients on first- or second-generation EGFR-TKI.
Higher (>= 2) ECOG performance status and longer (>= 10 months) time to
disease progression following EGFR-TKI treatment initiation were
associated with T790M positivity. Conclusions: Results from
plasma/tissue-cytology samples in a real-world setting, yielded a T790M
positivity rate lower than previous reports. Fewer than one in four
patients with negative plasma-based testing underwent tissue re-biopsy,
indicating the challenges in routine care settings.
ER -