Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
MA08: TREATMENT MONITORING IN ADVANCED NSCLC
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
MA08.07 PROSPECTIVE SEQUENTIAL COUNTS OF TOTAL CTC OR
CKIT+CTC IN ADVANCED NSCLC WITH 1ST LINE CHEMOTHERAPY
(POLICE)
Xu-Chao Zhang 1 , Zhen Wang 2 , Yan-Ming Deng 3 , Wei-Bang Guo 1 , Jin -Ji Yang 4 ,
Hong-Hong Yan 1 , Qing Zhou 4 , Binchao Wang 2 , Wei-Neng Feng 3 , Huajun Chen 4 ,
Hai-Yan Tu 2 , Li Zhang 5 , Xiaoqing Liu 6 , Qing-Feng Zou 7 , Yi Long Wu 2
1 Medical Research Center, Guangdong Lung Cancer Institute, Guangdong
General Hospital & Guangdong Academy of Medical Sciences, Guangzhou/China,
2 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong
Academy of Medical Sciences, Guangzhou/China, 3 Oncology, Foshan the First
People’S Hospital, Foshan/China, 4 Division of Pulmonary Oncology,cancer Center,
Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong
Academy of Medical Sciences, Guangzhou/China, 5 Department of Medical
Oncology, Sun Yat-Sen University Cancer Center, Guangzhou/China, 6 Department
of Pulmonary Oncology, 307 Hospital of the Academy of Military Medical Sciences,
Cancer Center, Beijing/China, 7 Cancer Center of Guangzhou Medical University,
Guangzhou/China
Background: Circulating tumor cells (CTCs) have been reported prognostic
and predictive in non-small cell lung cancer (NSCLC) and a few of other
cancer types. In 1 st line setting, whether EPCAM + CK + CD45 - CTC and/or stem
cell-like cKIT + EPCAM + CK + CD45 - CTC enumeration and dynamic changes can
be prognostic and/or predictive to standard chemotherapy need further
investigation in Chinese patients with NSCLC. Methods: A prospective study
on the CTC enumeration in advanced NSCLC with 1st line chemotherapy
(POLICE) was started by China Thoracic Oncology Group (CTONG). Patients
with NSCLC naïve for systemic regimens were enrolled since August 2013.
CTCs were detected by Cell Search Platform and identified as positive for
EPCAM + CK + CD45 - phenotype. CD117 (cKIT) marker was added to test the
frequency of stem cell-like cKIT + EPCAM + CK + CD45 - CTCs. Primary endpoints
were CTC counts and its correlation with first line therapy. Results: Totally
180 patients were enrolled. In 174 case total CTC and cKIT + CTC positive (cutoff
>=1) rates were 38.5% (67/172) vs 14.3% (24/168), 21.8% (31/142) vs 6.3%
(9/142), 13.7% (13/95) vs 6.4% (6/94) and 40.4% (38/94) vs 15.0% (13/93) at
time-points of baseline, after first-cycle-chemo, after four-cycles-chemo and
disease progression. At time immediately after first-cycle-chemo, patients in
CTC=0 group got statistically higher ORR (29.0% VS 7.1%, P=0.017) and DCR
(74.2% VS 42.9%, P=0.002) than in CTC>=1 group. At time after four-cycleschemo,
patients in CTC=0 group got statistically higher DCR (88.3% VS 58.3%,
P=0.026) than in CTC>=1 group. At time either after first-cycle-chemo or after
four-cycles-chemo, patients in CTC>=1 group got worse PFS (5.7m VS 4.0m,
P=0.025; 6.3m VS 4.0m, P=0.001 ) than in CTC=0 group. At time after firstcycle-chemo,
patients in groups cKIT + CTC>=1 and cKIT - CTC>=1 got worse PFSs
(3.1m vs 4.0m vs 5.7m, P=0.001) and worse DCRs (44.4% vs 42.1% vs 73.9%,
P=0.009) than in CTC=0 group. For 142 patients categorized into three groups
of dynamic CTC decrease (17), CTC unchanged (82), and CTC increase (43),
there were significant differences in terms of DCR (71.8% vs 71.6% vs 33.3%,
P=0.018) and PFS (5.2m vs 5.6m vs 3.1m, P=0.037). Conclusion: In first line
setting of advanced NSCLC, at time-points after first-cycle-chemo other than
baseline, total CTC or cKIT + CTC counts could be predictive for worse DCR or
PFS. CTC increase from baseline to after-first-cycle-chemo might be a strong
signal for the inefficacy of first line chemotherapy in the NSCLC patients.
Keywords: Circulating tumor cell, non-small cell lung cancer, predictive
marker, cKIT
MA08: TREATMENT MONITORING IN ADVANCED NSCLC
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
MA08.09 MONITORING PLASMA EGFR MUTATIONS DURING FIRST
LINE TREATMENT WITH EGFR TKIS IN NSCLC PATIENTS
Katja Mohorcic 1 , Izidor Kern 2 , Urska Janzic 1 , Nina Turnsek Hitij 1 , Mitja Rot 2 ,
Tanja Cufer 1
1 Medical Oncology Unit, University Clinic of Respiratory and Allergic Diseases
Golnik, Golnik/Slovenia, 2 Pathology Department, University Clinic of Respiratory
and Allergic Diseases Golnik, Golnik/Slovenia
Background: Genotyping cell free circulating DNA (cfDNA) is a non-invasive
method of detecting EGFR mutations (EGFRmu) in plasma and may provide an
option to identify patients who progress while treated with EGFR TKIs. The
aim of our study was to monitor plasma EGFRmu and identify dynamic case
specific changes in plasma EGFRmu during routine treatment of advanced
EGFRmu NSCLC patients. Methods: Plasma was collected from patients with
advanced EGFRmu NSCLC treated with first- or second-generation EGFR TKIs.
Plasma EGFRmu were dynamically monitored consecutively at every
scheduled visit. Cobas EGFR Mutation Test v1 and v2 (Roche, USA) was used to
detect 42 mutations at EGFR gene in exons 18 to 21. Liquid biopsy progression
(LBP) was determined as reappearance of EGFRmu in plasma after
negativisation during treatment or increase of EGFRmu levels expressed by
semi-quantitative index (SQI). Radiologic progression was determined in
accordance with RECIST1.1 criteria. Results: From May 2014, 23 patients were
treated with EGFR TKIs for advanced EGFRmu NSCLC; 20/23 had detectable
activating mutations in plasma before any treatment and were therefore
included in our analysis. Dynamic changes of plasma EGFRmu during 1 st line
EGFR TKI treatment are shown in Figure 1. Eight patients (40%) experienced
RECIST 1.1 progression while on treatment, whereas one patient was
inevaluable. In 4/8 patients (50%) LBP appeared at the same time as radiologic
progression, in 3/8 patients (37%) LBP appeared before radiologic progression
(8w, 14w, 20w before, respectively) and in 1 patient (12%) radiologic
progression appeared 6w before LBP. Among patients who did not experience
radiologic progression yet, some dynamic changes in cfDNA were also
observed, but alterations in the SQI values were much smaller.
Conclusion: Monitoring EGFR mutations in plasma is a feasible and less
invasive method in routine clinical practice and could be used as a predictive
marker of progression on treatment with EGFR TKIs.
Keywords: plasma EGFR mutations, NSCLC
TREATMENT MONITORING IN ADVANCED NSCLC
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
MA08.10 DETECTION OF THE T790M MUTATION OF EGFR IN
PLASMA OF ADVANCED NSCLC PATIENTS WITH ACQUIRED
RESISTANCE TO EGFR-TKI (WJOG8014LTR)
Koichi Azuma 1 , Takayuki Takahama 2 , Kazuko Sakai 3 , Masayuki Takeda 2 ,
Toyoaki Hida 4 , Masataka Hirabayashi 5 , Tetsuya Oguri 6 , Hiroshi Tanaka 7 ,
Noriyuki Ebi 8 , Toshiyuki Sawa 9 , Akihiro Bessho 10 , Motoko Tachihara 11 ,
Hiroaki Akamatsu 12 , Shuji Bandoh 13 , Daisuke Himeji 14 , Tatsuo Ohira 15 ,
Mototsugu Shimokawa 16 , Nobuyuki Yamamoto 12 , Yoichi Nakanishi 17 , Kazuhiko
Nakagawa 2 , Kazuto Nishio 3
1 Division of Respirology, Neurology, and Rheumatology, Department of Internal
Medicine, Kurume University School of Medicine, Kurume/Japan, 2 Department of
Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama/Japan,
3 Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-
Sayama/Japan, 4 Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya/Japan,
5 Hyogo Prefectural Amagasaki General Medical Center, Hyogo/Japan, 6 Nagoya City
University, Aichi/Japan, 7 Department of Internal Medicine, Niigata Cancer Center
Hospital, Niigata/Japan, 8 Department of Respiratory Oncology, Iizuka Hospital,
Fukuoka/Japan, 9 Cancer Center, Gifu Municipal Hospital, Gifu/Japan, 10 Respiratory
Medicine, Japanese Red Cross Okayama Hospital, Okayama/Japan, 11 Division
of Respiratory Medicine, Department of Internal Medicine, Kobe University
Graduate School of Medicine, Kobe/Japan, 12 Third Department of Internal Medicine,
Wakayama Medical University, Wakayama/Japan, 13 Kagawa University, Kagawa/
Japan, 14 Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital,
Miyazaki/Japan, 15 Thoracic Surgery, Tokyo Medical University Hospital, Tokyo/
Japan, 16 Clinical Research Institute, National Kyushu Cancer Center, Fukuoka/Japan,
17 Kyushu University, Fukuoka/Japan
Copyright © 2016 by the International Association for the Study of Lung Cancer
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