Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
The high-frequency mutations were PAK3-D219E, FBXW7-D112E, TET2-T418I,
KAT6A-E796A, and MET-R1005Q. However, the common mutations in other
NSCLC, like EGFR, KRAS, ALK, etc., weren’t happened in this group of PACC. In
this study, the spatial heterogeneity was discovered in PACC, not only in the
mutation site, but also in the mutant abundance. Moreover, the phylogenetic
relationships revealed that the clonal evolution and development existed in
PACC. Conclusion: The status of genomic alterations in PACC was different
from the other non-small cell lung cancer (NSCLC). PACC showed obvious
spatial heterogeneity and clonal evolution.
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
AGAINST LUNG CANCER SESSION
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
JCES01.16 A MET INHIBITOR IN THE TREATMENT OF METASTATIC
NON SMALL CELL LUNG CANCER WITH MET AMPLIFICATION
Tongtong Zhang 1 , Junling Li 2
1 Department of Medical Oncology, Cancer Institute & Hospital, Peking Union
Medical College/chinese Academy of Medical Science, Beijing/China, 2 Cancer
Institute & Hospital, Peking Union Medical College/chinese Academy of Medical
Science, Beijing/China
Background: Amplification of the mesenchymal-epithelial transition
factor (MET) gene plays a vital role in non-small cell lung cancer (NSCLC).
The anti-MET therapeutic strategies are still unclear in epidermal growth
factor receptor (EGFR) mutant patients and EGFR-naive patients. Aims
of our study are to discuss role of MET amplification in Chinese NSCLC
patients, and evaluate the antitumor activity of crizotinib (MET inhibitor)
in Chinese NSCLC patients with MET gene amplification. Methods: From
Jun 2015 to Jan 2016, we detected 11 metastatic NSCLC patients with MET
amplification by fluorescence in situ hybridization (FISH). MET amplification
was defined as gene focal amplification or high polysomy (at least 15% cells
with ≥5 copy numbers). Patients with MET de novo amplification received
crizotinib, patients with concomitant MET acquired amplification and EGFR
mutation received combined therapy of EGFR-tyrosine kinase inhibitors
(TKIs) (gefitinib, erlotinib, icotinib)and crizotinib. All enrolled subjects
received tumor measurement according to RECIST1.1 Results: The frequency
of MET de novo amplification was 54.5%(6/11), and that of concomitant MET
acquired amplification and EGFR mutation was 45.5%(5/11) respectively. 4 of
6 patients with MET de novo amplification received crizotinib, 2 patients had
partial response (PR), 1 patient had stable disease (SD), 1 patient died due to
heart disease. Response rate (RR) of crizotinib was 50%(2/4). Encouraging
response was observed in one case, a CT scan performed 31 days after starting
crizotinib revealed 42.2% decrease in tumor measurement, until now, a
7-month CT revealed 60.0% decrease. 3 of 5 patients with concomitant MET
acquired amplification and EGFR mutation received the combined therapy
of EGFR-TKIs and crizotinib. 1 patient achieved PR, 2 patients had SD. RR
of combined therapy was 33.3%(1/3). Dramatic response was observed in
one case with combined therapy, a 2-month CT revealed 31.0% decrease in
tumor measurement. Conclusion: According to our study, patients with MET
amplification benefited from crizotinib, and RR was inspiring. Patients with
concomitant MET acquired amplification and EGFR mutation need combined
targeted therapy.
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
AGAINST LUNG CANCER SESSION
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
JCES01.17 A PHASE I DOSE EXPANSION STUDY OF EPITINIB TO
EVALUATE EFFICACY AND SAFETY IN EGFR MUTATION POSITIVE
(EGFRM+) NSCLC PATIENTS WITH BRAIN METASTASIS
Qing Zhou 1 , Bin Gan 2 , Qunying Hong 3 , Mengzhao Wang 4 , Xiaoqing Liu 5 , Liwei
Yuan 6 , Ye Hua 7 , Hongcan Ren 6 , Weiguo Su 7 , Yi Long Wu 8
1 Guangdong Lung Cancer Institute; Guangdong General Hospital(GGH)&
Guangdong Academy of Medical Sciences, Guangzhou/China, 2 Guangdong Lung
Cancer Institute, Guangdong General Hospital (GGH)and Guangdong Academy
of Medical Sciences, Guangzhou/China, 3 Zhongshan Hospital, Shanghai Fudan
University, Shanghai/China, 4 Peking Union Medical College Hospital, Beijing/China,
5 Department of Pulmonary Oncology, 307 Hospital of the Academy of Military
Medical Sciences, Cancer Center, Beijing/China, 6 Hutchison Medipharma Ltd,
Shanghai/China, 7 Hutchison Medipharma Limited, Shanghai/China, 8 /
Background: A significant portion of patients with non-small cell lung cancer
(NSCLC) develop brain metastasis. Patients with brain metastasis suffer
from poor prognosis with a median survival of less than 6 months and low
quality of life with limited treatment options. First generation EGFR tyrosine
kinase inhibitors (EGFR TKIs) have demonstrated significant clinical benefit
for patients with EGFR-mutant NSCLC. However, their effect on brain
metastasis is limited due to poor drug penetration into the brain. Epitinib is
an EGFR TKI designed to improve brain penetration. A Phase I dose escalation
study on epitinib has been completed and the recommended Phase 2 dose
(RP2D) determined (Y-L Wu, 2016 ASCO). This Phase I dose expansion study
was designed to evaluate the efficacy and safety of epitinib in EGFR-mutant
NSCLC patients with brain metastasis. Methods: This is an ongoing open
label, multi-center Phase I dose expansion study. EGFR-mutant NSCLC
patients with confirmed brain metastasis, either prior EGFR TKI treated or
EGFR TKI treatment naïve, were enrolled to receive oral epitinib 160 mg per
day. Patients with extra-cranial disease progression while on treatment
with an EGFR TKI were excluded. Tumor response was assessed per RECIST
1.1. Results: As of 31 May, 2016, 27 patients (13 EGFR TKI pretreated, 14 EGFR
TKI treatment naïve) have been enrolled and treated with epitinib. The most
frequent adverse events (AEs) were skin rash (89%), elevated ALT (41%)/AST
(37%), hyper-pigmentation (41%) and diarrhea (30%). The most frequent
Grade 3/4 AEs were elevations in ALT (19%), gamma-GGT (11%), AST (7%),
hyperbilirubinemia (7%) and skin rash (4%). There have been no Grade 5 AEs
to date. Among the 24 efficacy evaluable patients (11 TKI pretreated, 13 TKI
naïve), 7 (7/24, 29%) achieved a partial response (PR), including 1 unconfirmed
PR. All PRs occurred in EGFR TKI treatment naïve patients (7/13, 53.8%). Of the
24 evaluable patients, 8 (5 EGFR TKI treatment naïve, 3 EGFR TKI pretreated)
had measurable brain metastasis (lesion diameter>10 mm per RECIST 1.1)
with 2 PRs (both EGFR TKI treatment naïve patients, 2/5, 40%). Conclusion:
Epitinib 160mg per day treatment in EGFR-mutant NSCLC patients with
brain metastasis demonstrated clinical activity both extra- and intra-cranial.
Epitinib was well tolerated. The data to date appears encouraging and
warrants further development of epitinib.
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
AGAINST LUNG CANCER SESSION
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
JCES01.18 DUAL POSITIVE PD-L1 AND CD8+ TIL REPRESENTS A
PREDOMINANT SUBTYPE IN NSCLC AND CORRELATES WITH
AUGMENTED IMMUNOGENICITY
Si-Yang Liu 1 , Zhong-Yi Dong 2 , Wen-Zhao Zhong 3 , Si-Pei Wu 1 , Zhi Xie 2 , Hai-Yan
Tu 4 , Yi Long Wu 5
1 Guangdong Lung Cancer Institute; Guangdong General Hospita & Guangdong
Academy of Medical Sciences, Guangzhou/China, 2 Guangdong Lung Cancer
Institute, Guangdong General Hospital, Guangzhou/China, 3 Department of
Pulmonary Oncology, Guangdong General Hospital & Guangdong Academy
of Medical Sciences, Guangzhou/China, 4 Guangdong Lung Cancer Institute,
Guangdong General Hospital & Guangdong Academy of Medical Sciences,
Guangzhou/China, 5 /
Background: Recent studies have identified that the degree of tumor
infiltrating lymphocyte (TIL) infiltration and PD-L1 expression in the tumor
microenvironment (TME) are significantly correlated with the clinical
outcomes of anti-PD-1/PD-L1 therapies. Here we conducted this study to verify
the distribution of PD-L1/CD8 + TIL expression and its clinical significance in
non-small cell carcinoma (NSCLC). Potential mechanism predicted for PD-1
blockade was explored in depth as well. Methods: Immunohistochemistry
was performed to detect PD-L1 and CD8 expression in NSCLC. The Kaplan–
Meier (KM) survival curve was used to estimate disease free survival (DFS)
and overall survival (OS). Gene Set Enrichment Analysis (GSEA) was used to
determine potentially relevant gene expression signatures.
Results: 288 cases with stage I-IIIA NSCLC were evaluated for PD-L1 and
CD8+ TIL staining. Dual positive PD-L1 and CD8 (PD-L1+/CD8+) represents a
predominant subtype in NSCLC, accounting for 36.5% (105/288), followed by
PD-L1-/CD8- (24.3%, 70/288), PD-L1-/CD8+ (26.0%, 75/288) and PD-L1+/CD8-
(13.2%, 38/288). Survival analysis of DFS (p=0.031) and OS (p=0.002) showed
a significant difference between four subgroups. Furthermore, we analyzed
the correlation between expression types of PDL1/CD8 and mutation burden
and angtigen presentation. We can identified dual positive PD-L1 and CD8
was significant with increased mutation burden (p