Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
1 Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences,
New Delhi/India, 2 Biochemistry, Maulana Azad Medical College, New Delhi/India,
3 Biochemistry, All India Institute of Medical Sciences, New Delhi/India, 4 Dept of
Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences,
New Delhi/India
Background: Targeted therapy with tyrosine kinase inhibitors (TKI) in EGFR
positive patients is associated with superior response rates in Caucasian and
East Asian populations. Whether similar response is observed in Asian Indians
with lung cancer is not yet clear. We aimed to compare the response rates
and survival between EGFR positive and negative patients with advanced
adenocarcinoma lung at a tertiary level centre in North India. Methods:
Treatment naive patients of adenocarcinoma lung were recruited. All patients
underwent complete staging and tissue EGFR mutation analysis using DNA
extraction and Polymerase chain reaction. EGFR positive patients were
treated with oral Gefitinib 250 mg once daily and EGFR negative patients
with 3-weekly cycles of platinum based doublet chemotherapy. Treatment
response was evaluated after 3 months of Gefitinib or after 4 cycles of
chemotherapy using CT-PET scan and categorized as Complete metabolic
remission (CR), partial response (PR), stable disease (SD), and progressive
disease (PD). The proportion of responders (CR + PR) and non-responders
(SD+PD), and short term survival at 3 months were compared between EGFR
positive and negative patients. Results: 59 patients completed response
evaluation at 3 months / 4 cycles. These included 41 males (59.5%), with a
mean (SD) age 55.9 (11.2) years. Majority (89.4%) had metastatic stage IV
disease. 34 patients (67.5%) were current or previous smokers, with median
smoking index of 400 (range, 0-1500). 76% patients had KPS of 80 or above,
and 78% had ECOG of 0-1. Overall, 17 patients (29.3%) were tissue EGFR
positive for either of exons 18, 19, or 21. The 3-month outcomes in EGFR
positive and negative groups were: complete response – 1.6% vs 0 %, partial
response - 61 % vs 24.4%, stable disease – 5.6% vs 26.8%, progressive disease
– 11.1% vs 17.1%, and mortality in 16.7% vs 31.7% respectively. EGFR positive
group had higher responders compared to EGFR negative patients (p=0.002)
although mortality rate did not differ significantly. Conclusion: EGFR
mutation positive patients treated upfront with TKI are more likely to show
objective response at three months and demonstrate a trend towards lower
mortality compared to EGFR negative patients treated with conventional
chemotherapy.
Keywords: Adenocarcinoma, EGFR mutation, responder, lung cancer
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-038 MOLECULAR DYNAMICS SIMULATION OF EFGR L844V
MUTANT SENSITIVE TO AZD9291 IN NON-SMALL CELL LUNG
CANCER
Vahideh Assadollahi 1 , Behnam Rashidieh 2
1 Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj/
Iran, 2 Griffith University & Qimr Berghofer Medical Research Inc, Brisbane/ACT/
Australia
Background: The Epidermal growth factor receptor (EGFR) belongs
to the ErbB family of Receptors of Tyrosine Kinases (RTK) containing
transmembrane domain, an extracellular ligand-binding domain and
intracellular region which the tyrosine-kinase region which has activity
for signal transduction. EGFR has a critical role in the efficient control of
growth, proliferation, survival and differentiation in cells. Approximately
half of cases of triple-negative breast cancer (TNBC) and inflammatory breast
cancer (IBC) overexpress EGFR. In many other cancers namely, lung and
colon cancer the overexpression of this receptor has been observed as well.
In more than 60% of non-small cell lung carcinomas (NSCLCs) mutation in
EFGR has been occurred, so EGFR also has become an important therapeutic
target for the treatment of these tumors. In recent years, designing drugs to
inhibit the activity of this receptor in cancer cells has been on the agenda of
Precision Medicine Scientists. Such treatment so called targeted therapy is
considered as a new approach to treat cancer, in which the treatment is more
effective, specific and has fewer side effects for the patient. These drugs are
inhibitors that block extracellular protein or impair a part of Tyrosine kinase
activity (TKIs). It is essential to note that mutations in EGFR limit the use of
these medications; thus, so far three generations of these drugs have been
developed to inhibit the Tyrosine kinase activity. The first generations of
Tyrosine kinase inhibitors are used in the treatment of patients who have a
L858R mutant in EGFR. The second-generation drug could overcome T790M
mutation. AZD9291 belongs to third-generation drug and is a potent, selective
and irreversible inhibitor of both EGFR sensitizing and T790M resistance
mutations with less activity towards wild-type EGFR. This drug overcomes
the T790M mutation, in addition to the fact that it can overcome sensitive
mutants such as L844V. L844V is a mutation in the drug resistant cells and did
not lead to constitutive EGFR phosphorylation. Methods: This study examines
how AZD9291 drug interact with EGFR protein kinase in L844V mutant with
adopting docking and dynamic molecular simulation using Gromacs software
version 4.5.6 to understand how this protein develop sensitive against the
mentioned drug. Results: The results of the analysis of RMSD simulation in
thirty nanoseconds confirm that the assumptions of the study is correct.
Conclusion: AZD9291 as a new inhibitor seem to form a stable interaction with
the L844V mutant.
Keywords: EGFR, L844V, AZD9291, Molecular dynamics simulation, Docking,
NSCLC
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-039 ANALYSIS OF PROGNOSTIC FACTOR FOR AFATINIB
TREATED PATIENTS WITH EGFR MUTATION POSITIVE NSCLC
Masafumi Sata 1 , Terufumi Kato 1 , Saki Manabe 2 , Shuji Murakami 1 , Tetsuro
Kondo 2 , Haruhiro Saito 1 , Akimasa Sekine 3 , Takashi Ogura 3 , Kouzo Yamada 2
1 Thoracic Oncology, Kanagawa Cancer Center, Yokohama/Japan, 2 Department
of Thoracic Oncology, Kanagawa Cancer Center, Yokohama/Japan, 3 Respiratory
Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama/Japan
Background: Afatinib, known as irreversible EGFR-TKI, significantly
improved PFS and OS versus cisplatin-based chemotherapy, in combined
analysis of LUX-Lung 3 and 6 despite this was not proved in treatment with
former reversible agents. We have tried to examine the factors correlated
to improvement of survival in patients treated with afatinib compared
to gefitinib or erlotinib. Methods: Patients who are enrolled in clinical
trials from 2008 to 2014, and treated with EGFR-TKI as first line treatment
were eligible. To explore the prognostic factors, we analyzed correlation
of candidate factors including age, sex, clinical stage, mutation type and
subsequent systemic treatments on medical record in afatinib treated
group and reversible agents treated group including gefitinib or erlotinib.
Results: Nineteen patients (5 men, 14 women) with a median age of 62 years
(range, 46-88 ) were treated with EGFR-TKI as first line treatment. Twelve
patients were treated with reversible TKIs, 8 with gefitinib, 4 with erlotinib.
Seven patients were treated with afatinib. Median PFS for reversible TKI
group versus afatinib group was 397 vs 422 days (P = 0.810). Median OS for
reversible TKI group versus afatinib group was 741 vs 1380 days (P = 0.501).
There is no difference between the two groups, age(P=0.147), sex(P=0.211),
stage(P=0.891), and mutation type(P=0.581). Eleven patients received
subsequent EGFR-TKI after first line EGFR-TKI failed as “re-challenge”, 7
patients in reversible TKI group, and 4 patients in afatinib group. There is no
difference of tumor response of “re-challenge” EGFR-TKI, and duration of
treatment with EGFR-TKI, in two groups. Conclusion: The patient treated with
afatinib tends to live longer in terms of overall survival. But there were no
significant correlated factor between clinical characteristics and duration of
survival.
Keywords: EGFR-TKI, prognotic factor
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-040 A COMPARISON OF DDPCR AND ARMS FOR DETECTING
EGFR T790M STATUS FROM ADVANCED NSCLC PATIENTS WITH
ACQUIRED EGFR-TKI RESISTANCE
Wenxian Wang 1 , Zhengbo Song 2 , Yiping Zhang 3 , Ying Jin 4
1 Chemotherapy, Zhejiang Cancer Hospital, Zhejiang/China, 2 Chemotherapy,
Zhejiang Cancer Hospital, Hangzhou/China, 3 Chemotherapy, Zhejiang Cancer
Hospital, Hangzhou,zhejiang/China, 4 Zhejiang Cancer Hospital, Hangzhou/China
Background: To assess the ability of droplet digital PCR and ARMS technology
to detect epidermal growth factor receptor (EGFR) T790M mutations from
circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC)
patients with acquired EGFR-TKI resistance. A sensitive and convenient
method for detecting T790M mutation would be desirable to direct patient
sequential treatment strategy.To assess the ability of droplet digital PCR
and ARMS technology to detect epidermal growth factor receptor (EGFR)
T790M mutations from circulating tumor DNA (ctDNA) in advanced nonsmall
cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance.
A sensitive and convenient method for detecting T790M mutation would
be desirable to direct patient sequential treatment strategy. Methods: A
comparison of two platforms for detecting EGFR mutations in plasma ctDNA
was undertaken. Plasma samples and tumor samples were collected from
Copyright © 2016 by the International Association for the Study of Lung Cancer
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