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OBSERVATIONAL POST-AUTHORIZATION PROSPECTIVE STUDY TO CHARACTERIZE THE INCIDENCE OF EGFR POSITIVE MUTATION (M+) IN ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER
(aNSCLC) PATIENTS (P) AND THEIR CLINICAL MANAGEMENT IN GALICIA (NCT01717105): A GALICIAN LUNG CANCER GROUP STUDY (GGCP 048-10)
Sergio Vázquez Estévez1, Joaquín Casal Rubio2, Javier Afonso Afonso3, José Luis Fírvida Pérez4, Lucía Santomé Couto5, Francisco Barón Duarte6, Martín Lázaro Quintela7, Carolina Pena Álvarez8, Margarita Amenedo Gancedo9, Ihab Abdulkader Nallib6,
Carmen González Arenas10, Laura Fachal11, Ana Vega11
1 Hospital Universitario Lucus Augusti (Lugo); 2 Complexo Hospitalario Universitario de Vigo (Pontevedra); 3 Hospital Arquitecto Marcide de Ferrol (A Coruña); 4 Complexo Hospitalario Universitario de Ourense; 5 Hospital Povisa de Vigo (Pontevedra); 6 Complexo Hospitalario Universitario de Santiago (A Coruña); 7 Complexo Hospitalario Universitario de Vigo (Pontevedra); 8 Complexo Hospitalario de
Pontevedra; 9 Centro Oncolóxico de Galicia (A Coruña); 10 AstraZeneca, Madrid, Spain; 11 Fundación Pública Galega de Medicina Xenómica-SERGAS, Santiago de Compostela, Spain
BACKGROUND
 Primary Objective:
 To characterize the number of patients with epidermal growth
factor receptor (EGFR) positive mutations among advanced or
metastatic non-small cell lung cancer (NSCLC) patients in Galicia
 Secondary Objective:
 To describe the type of mutations among NSCL EGFR M+ patients.
 To describe the clinical management of EFGR M+ patients.
 To describe patterns of EGFR mutations after progression of EGFR
M+ patients.
 To correlate EGFR mutational status in tumour and serum samples.
 To compare EGFR mutational status between baseline and disease
progression of EGFR M+ patients.
Table 1: Baseline Characteristics
Characteristic
Total Patients
N=198
Characteristic
Male
151 (76.3%)
Smoking status
Female
47 (23.7%)
Ex-smoker
90(45.5%)
Age
Median
65.5 years
Smoker
65 (32.8%)
Histology
Squamous
43 (21.7%)
0
27 (13.6%)
Adenocarcinoma
136 (68.7%)
1
106 (53.5%)
Large cells Carc.
16 (8.1%)
2
49 (24.7%)
Adenosquamous
2 (1.0%)
≥3
16 (8.1%)
NOS
1 (0.5%)
Sex
WHO PS
Total Patients
N=198
Never smoked
43(21.7%)
Table 2: Sample source and type
Patients EGFR M+
Figures 3 & 4: Line of Treatment for Patients EGFR M+
N=25
13.6%1
0
11
11
2
1
1
12
11
1
0%2
44%2
Exon 18
Exon 19
Del 19
Exón 20
Exon 20 insertions
Not specificed
Exon 21
L858R
L681Q
All
newly
diagnosed
aNSCLC patients in 9
Galician
centres
were
prospectively included for a
13-month period.
Patients with M+ disease
were
followed
from
inclusion
until
disease
progression, death or until 9
months from the inclusion
of the last patient in the
study
have
elapsed,
whichever is earlier, for the
characterization of their
clinical management
Figure 1: Flowchart
Mutation testing was performed on available tumour and serum
samples, through a central laboratory using the EGFR RGQ PCR KitTM
(Qiagen)
Pre-planned exploratory objectives included comparison of EGFR
mutation status between matched baseline tumour and plasma samples
4%
TKI (Gefitinib)
4%
Best suportive care
QT (CDDP+Doc+Bev)
Active Treatment
QT+TKI
(Carbo+Gefitinib)
92%
48%2
92%
Figure 5: First Line Treatment Response rate
Out of the 23 patients that underwent treatment 3 were excluded due to lost of
follow up and only 20 were evaluated
Figure 2: EGFR Mutation Rates by Clinical features
78,9%
First Line Treatment (N=23)
8%
8%2
71,4%
70
Never smoked
57,6%
60
50
42,4%
40
Female
% Tissue
38,60%
19,80%
Adenocarcinoma
28,6%
21,1%
20
Ex-smoker
7,10%
Male
0
Primary tumor
Metastatic site
60%
Male
50%
Ex-smoker
40%
Adenocarcinoma
30%
Female
20%
Never smoked
10%
Smoker
10%
3,40%
PR
Table 6: Comparison of baseline tumour EGFR mutation status
with evaluable results from baseline serum
Average: 10.3 days
Table 4: Mutation frequency by sample type
Biopsy
N=108
20%
0%
Median: 8 Working days
Total
N=184 (%)
5,70%
Smoker
Total
Table 3: Turn Around Time (TAT)
EGFR Status
70%
70%
% Cytology
30
80%
42,50%
10
METHODS
Percentage of Patients EGFR M+
(N=25) Ongoing Active Treatment
(1) Percentage calculated considering n=184 samples evaluable for EGFR Status;
(2) Percentage according to Patients EGFR M+
90
80
Table 5: Types of Mutation
EGFR status at
baseline
Cytology
N=76
EGFR +
25 (13.6%)
15 (13.9%)
10(13.2%)
EGFR -
159 (86.4%)
93 (86.1%)
66 (86.8%)
Tumor
mutation
status
Serum mutation status
Concordance rate
90.8%
EGFR +
EGFR -
Total
Sensitivity
40%
EGFR +
10
15
25
Specificity
99.3%
EGFR -
1
148
149
Positive predictive value (PPV)
90.9%
Negative predictive value (NPV)
90.8%
Total
11
163
174*
*Summary of EGFR status for tumour and serum samples from patients who are evaluable for both samples.
CONCLUSIONS
SD
PD
Figures 6 and 7: PFS & OS For Patients EGFR M+ (n= 20 )
Progression free survival (PFS)
1,0
Median (months) 95% CI
9.74
4.02-15.50
0,8
12-month PFS: 37% (95% CI: 15.3-58.8)
0,6
0,4
0,2
0,0
0
5
10
15
Overall survival (OS)
1,0
20
Estimated probality of overall survival
OBJECTIVES
 From February 2011 to March 2012 a total of 198 patients were enrolled
 Mutation analysis in tissue samples was feasible in 184 P (92.93%)
Estimated probability of PFS
The presence of mutations in the gene encoding the Epidermal Growth
Factor Receptor (EGFR) predicts that P with aNSCLC may respond better to
Tyrosine Kinase Inhibitors (TKIs)1-4. Recently, the Spanish study REASON has
reported that the rate of EGFR mutations is 11.6% in Spain5, however the
mutation rate and the clinical management of aNSCLC patients carrying
EGFR mutations in Galicia are still unknown.
RESULTS
Median (months)
0,8
17.80
95% CI
7.31-28.28
0,6
0,4
0,2
0,0
0
5
Time from first line treatment (months)
10
15
20
25
Time from first linetreatment (months)
The estimated prevalence of EGFR mutations in a representative sample of newly diagnosed advanced NSCLC patients in Galicia is
BIBLIOGRAPHY
consistent with previous data obtained in the rest of Spain
EGFR mutation testing was possible in more than 90% of patients.
1. Mok TS et al. N Engl J Med 2009;361:947-957.
Given the similar adequacy for molecular analysis and mutation rates observed in cytological vs. tissue samples, cytologies should
2. Maemondo M et al. N Engl J Med 2010;362:2380-2388.
3. Mitsudomi T et al. Lancet Oncol 2010;11:121-128.
be considered suitable for mutation analysis.
4. Rosell R et al. N Engl J Med 2009;13: 239-246.
The median TAT of 8 days to establish the EGFR mutation status allows the customization of treatment based on molecular criteria
5. Massuti B et al. J Thorac Oncol 2011; 5 (Suppl 2): S329-S330, Abs.O12.07
EGFR testing in serum has a low sensitivity and therefore should not substitute tissue testing although it could be an alternative for
6. Rekhtman N, et al. J Thorac Oncol 2011; 6: 451–458.
those patients without tissue samples.
ACKNOWLEDGEMENTS
More than 90% of patients receive first line treatment, most of them received a TKI
Comparison EGFR mutational status between baseline and disease progression could not be done because no obtional tumor Patients and families, investigators, data managers, lab staff.
samples were obtained at progression.
This study was supported by AztraZeneca through the Investigators Sposored Studies programme
Poster presented at 15 WCLC , October 27-30 October , 2013. Sydney, Australia
th