Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
xenografting with PC-9/wt and PC-9/afa cells, oral administration of WZ8040
(50 mg/kg) consistently reduced the tumor growth of PC9/wt and PC-9/afa
cells. Conclusion: T790M mutation is the dominant resistant mechanism of
afatinib resistant EGFR mutant PC9/afa cells and use of 3rd generation EGFR
TKI successfully reversed afatinib resistance in PC9/afa cells.
Keywords: Epidermal growth factor receptor, afatinib, Resistance, non-small
cell lung cancer
(range, 38 – 86 years) were treated with osimertinib between 28 March and 30
June, 2016. Thirteen of the patients had no pleural effusion, of which twelve
were evaluable for tumor response and all of these experienced efficacies in
terms of response and stable disease. Twelve out of 25 patients had pleural
effusion, of which ten patients were evaluable; of these, nine patients had no
progression and one patient had progression during a short period of
treatment with osimertinib. Regarding the pleural effusion in these ten
patients, the effusion decreased in two patients and, was stable in three
patients; in five patients, these was a slight or moderate increase despite
daily administration of osimertinib. The long-term effects of treatment with
osimertinib will be presented in detail at the meeting.
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR RES –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-123 LYSIMACHIA CAPILLIPES CAPILLIPOSIDE INHIBITS AKT
ACTIVATION AND RESTORES SENSITIVITY TO GEFITINIB IN NSCLC
WITH ACQUIRED GEFITINIB RESISTANCE
Shirong Zhang 1 , Yasi Xu 1 , Er Jin 2 , Lucheng Zhu 3 , Bing Xia 4 , Xufeng Chen 5 ,
Shenglin Ma 6
1 Center for Translational Medicine, Hangzhou First People’s Hospital, Nanjing
Medical University, Hangzhou/China, 2 Departments of Respiratory Medicine,
Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou/China,
3 Department of Radiation Oncology, Hangzhou First People’s Hospital, Nanjing
Medical University, Hangzhou/China, 4 Department of Radiation Oncology,
Hangzhou Cancer Hospital, Hangzhou/China, 5 University of California at Los
Angeles, California/CA/United States of America, 6 Department of Oncology,
Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou/China
Background: Most non-small cell lung cancer (NSCLC) patients responding
to gefitinib will eventually develop the resistance. Lysimachia capillipes
(LC) capilliposide extracts from LC hemsl shows both in vitro and in vivo
anti-cancer effects. We investigated whether LC capilliposide combined
with gefitinib could overcome the resistance of NSCLC cells to gefitinib,
and to identify the involved molecular signaling. Methods: NSCLC cell lines
with different sensitivities to gefitinib were studied. Cell proliferation was
assessed with MTT assay. Cell apoptosis and cell cycle distribution were
measured using cytometry. EGFR-related signaling proteins and Human
Phospho-Kinase were analyzed using Western blotting and protein array,
respectively. Tumor growth inhibition were evaluated in PC-9-GR xenograft.
CC3, Ki67 and pEGFR were assessed by IHC on tumor tissues. Results: LC
capilliposide inhibited cell growth in gefitinib-sensitive and -resistant cells.
In gefitinib resistant cell PC-9-GR with T790M mutation, the LC capilliposide
combined with gefitinib was potent in cell growth inhibition and apoptosis
induction, but no obvious effect on gefitinib-induced G0/G1 arrest. LC
capilliposide remarkable blocks the phosphorylation of EGFR downstream
signaling molecule AKT, on which LC capilliposide and gefitinib alone had
no obvious effect. The Human Phospho-Kinase array further confirmed the
enhanced inhibitory effect on the AKT signaling. LC capilliposide treatment
also enhanced tumor growth inhibition when combined with gefitinib in
PC-9-GR xenografts. Conclusion: LC capilliposide restored the sensitivity to
gefitinib in NSCLC cells with acquired gefitinib resistance, suggesting that
combination of LC and gefitinib may be a promising therapeutic strategy to
overcome gefitinib resistance in NSCLCs with T790M mutation.
Keywords: Lysimachia capillipes Capilliposide, non-small cell lung cancer,
Gefitinib resistance, AKT
Conclusion: Although an active agent in clinical practice, osimertinib might
not provide an early response for pleural effusion.
Keywords: Osimertnib, pleural effusion, EGFR T790M
POSTER SESSION 3 – P3.02b: ADVANCED NSCLC & CHEMOTHERAPY/
TARGETED THERAPY/IMMUNOTHERAPY
EGFR RES –
WEDNESDAY, DECEMBER 7, 2016
P3.02b-125 Failure to Tyrosine Kinase Inhibitors and Patterns of Progression
in Patients with Advanced Non-Small Cell Lung Cancer
Feliciano Barron 1 , Laura-Alejandra Ramirez-Tirado 1 , Enrique Caballe-Perez 1 ,
Gisela Sanchez 1 , Andrés Cardona 2 , Oscar Arrieta 3
1 Thoracic Oncology Unit and Laboratory of Personalized Medicine, Instituto
Nacional de Cancerología, Mexico City/Mexico, 2 Clinical and Translational
Oncology Group, Clinica Del Country, Bogotá/Colombia, 3 Thoracic Oncology Unit
and Laboratory of Personalized Medicine, National Cancer Institute, Mexico City/
Mexico
Background: Some studies have evaluated the impact of patterns of
progression after treatment with tyrosine kinase inhibitors (TKI) in non-small
cell lung cancer (NSCLC). We evaluated the patterns of progression and
prognosis of NSCLC patients that received TKI. Methods: Using the criteria
established by Yang to define models of progression to TKI we did a
retrospective analysis. Survival curves were plotted using the Kaplan-Meier
method. The Cox proportional hazard model was used for multivariate
analysis. Results: Eighty-three NSCLC patients were included: 43 patients
with dramatic-progression (51.8%), 26 with gradual-progression (31.3%), and
17 with local-progression (16.9%); demographic and clinical characteristics
were similar in all subgroups. There was a significant difference in the median
Progression-Free Survival (PFS) among the three groups, for the group with
dramatic-progression it was 9.1 months, 16 months for gradual-progression
and 11.9 for local-progression (P: 0.044). The overall survival (OS) was different
among the three groups, for patients in gradual-progression 56 months, for
patients in dramatic-progression 30 months and local-progression 36.4
months (figure A). Additionally 41.7% were treated with afatinib after
progression to erlotinib and gefitinib. PFS in all patients was 8.08 months.
Patients that present asymptomatic progression have a longer OS compared
to those who present symptomatic progression (42 vs 31.9 months; p = 0.048).
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR RES –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-124 EFFICACY OF OSIMERTINIB IN PATIENTS WITH NON-
SMALL-CELL LUNG CANCER (NSCLC) AND PLEURAL EFFUSION
Saki Manabe 1 , Masafumi Sata 1 , Shuji Murakami 1 , Tetsuro Kondo 1 , Terufumi
Kato 1 , Haruhiro Saito 1 , Akimasa Sekine 2 , Takashi Ogura 2 , Kouzo Yamada 1
1 Thoracic Oncology, Kanagawa Cancer Center, Yokohama/Japan, 2 Respiratory
Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama/Japan
Background: Although epidermal growth factor receptor (EGFR) tyrosine
kinase inhibitors (TKIs) are effective in patients with mutated non-small-cell
lung cancer (NSCLC), pleural or pericardial effusion is a known negative factor
in EGFR-TKI monotherapy. Osimertinib, a 3rd-generation EGFR-TKI is an active
agent for treating EGFR T790M-positive NSCLC. We analyzed the efficacy of
osimertinib in EGFR T790M-positive patients with pleural effusion. Methods:
Patients treated with osimertinib were evaluated in clinical practice following
approval of the drug in Japan. Treatment responses of tumor and effusion
were measured and analyzed in patients with and without pleural effusion.
Results: Twenty-five patients (7 men, 18 women) with a median age of 70 years
S666 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017