Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
Jiahui Si, Panpan Zhang, Yang Yue
Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute,
Beijing/China
Background: Despite a consistent rate of initial responses, chemotherapy
treatment often results in the development of chemoresistance, leading to
therapeutic failure in non-small cell lung cancer (NSCLC). CMTM1_v17 is highly
expressed in human testis tissues and solid tumor tissues but relatively low
expression was obtained in the corresponding normal tissues. This study aims
to investigate the significance of CMTM1_v17 in NSCLC and its association
with cisplatin-based neo-adjuvant chemotherapy (NAC) response Methods:
31 pairs of tumor tissues before and after NAC and 78 resected tumor tissues
after NAC were utilized for immunohistochemistry (IHC) staining of CMTM1_
v17 protein. Flow cytometry was used to detect the change of CMTM1_v17
expression in NSCLC patient-derived xenografts (PDX models) with cisplatin
treatment. Results: CMTM1_v17 expression was found to be significantly
related to treatment effect and outcome in the tumor tissues after NAC but
not in the tissues before NAC from the 31 cases of NSCLC. We identified that
high CMTM1_v17 expression was associated with low objective remission
rate (ORR) (p=0.008) and poor prognosis (the median OS: 35.1 months vs 65.6
months,p=0.0045;the median DFS: 17.27 months vs 35.54 months,p=0.0207)
in the 31 patients. Next, we detected CMTM1_v17 expression to confirm
correlation between this protein status and clinical characteristics in 78
NSCLC patients with NAC. The up-regulation of CMTM1_v17 had a higher
SD rate (p=0.007) and worse outcome ( the median OS: 41.0 months vs 80.6
months, p=0.0028;the median DFS: 33.4 months vs 64.8 months,p=0.0032).
COX multivariate analysis indicated that CMTM1_v17 is an independent
prognostic risk factor on patients who received NAC (OS:HR=3.642,p=0.002
;DFS:HR=2.867,p=0.003). Then, we tested CMTM1_v17 expression in the lung
cancer PDX mice with different treatment, showing that this protein was upregulated
in the tumor tissues received cisplatin treatment, compared to the
tumor tissues with saline stimulation of control group. Conclusion: CMTM_v17
expression was significantly associated with chemoresistance and poor
prognosis of the early stage NSCLC patients who received NAC. Cisplatin could
induce the expression of CMTM1_v17 in lung cancer cells from PDX model.
Keywords: non-small cell lung cancer, CMTM1_v17, Cisplatin, neo-adjuvant
chemotherapy
POSTER SESSION 2 – P2.03A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
CLINICAL TRIALS –
TUESDAY, DECEMBER 6, 2016
P2.03A-052 PHASE I STUDY AND PHARMACOKINETICS OF
PACLITAXEL MICELLES FOR INJECTION IN CHINESE PATIENTS WITH
ADVANCED-STAGE MALIGNANCIES
Meiqi Shi 1 , Jing Sun 2 , Shaorong Yu 1 , Guohao Xia 1 , Li Wang 1 , Jifeng Feng 1
1 Jiangsu Cancer Hospital, China, Nanjing/China, 2 Institute of Biological Engineering,
East China University of Science and Technology, Shanghai/China
Background: Paclitaxel micelle for injection is a Cremophor-free, nanoscale,
polymer micelles loaded paclitaxel formulation. The absence of Cremophor EL
may permit Paclitaxel Micelle to be administered without the premedications
used for the prevention of hypersensitivity reactions. The objective of this
Phase I trial were to determine the toxic effects, maximum tolerated dose
(MTD), Dose-limiting toxicity (DLT), pharmacokinetics(PKs) profile and
recommended phase II dose of Paclitaxel Micelle. Methods: Dose escalation
of paclitaxel micelle for injection followed the standard “3+3” rule, and
started at does level 175 mg/m2. Eligible patients were treated with paclitaxel
micelle given as a 3 h intravenous infusion on day 1 once every 3 weeks. Blood
samples were collected to determine the PKs of paclitaxel micelle. Results:
18 patients with advanced malignancies were enrolled and treated, including
non-small cell lung cancer (NSCLC) 17 patients and breast cancer 1 patients.
The dose of paclitaxel micelle for injection ranged from 175 mg/m2 (dose
level 1) to 435 mg/m2 (dose level 5). All patients were evaluable for toxicity
and antitumor response. The most common toxic reactions of paclitaxel
micelles include neutropenia, peripheral nerve numbness and muscle pain,
no acute hypersensitivity reactions were observed. DLT included grade 4
neutropenia, which occurred in 1 of 6 patients treated at 300 mg/m2 (level
3) and all of 3 patients at 435 mg/m2 (level 5), and grade 3 peripheral nerve
numbness in 1 patient at 435 mg/m2 (level 5). The MTD was thus determined
to be 390mg/m2 (level 4). Partial response was observed in 6 of 18 patients
(33.3%), 3 of whom had prior exposure to paclitaxel chemotherapy. 9 patients
(50%) had stable response and only 3 patients had disease progression. 18
patients completed 99 cycles of paclitaxel micelle chemotherapy (2~19 cycles),
and now one patient at 390 mg/m2 (level 4) has been completed 19 cycles
of chemotherapy and is still in treatment. The median PFS was 9.1months
(95% CI,4.70-18.43). The paclitaxel Cmax and area under the curveinf values
increased with escalating doses, which revealed paclitaxel micelles has
linear PKs. Conclusion: In this study, Paclitaxel Micelles was administered
safely without premedication for preventing hypersensitivity reactions and
showed higher paclitaxel MTD without additional toxicity, which are more
advantageous than conventional paclitaxel formulation in clinic treatment.
Therefore, the recommended dose for the phase II study is 300 mg/m2.
Keywords: Drug toxicity, maximum tolerated dose, Paclitaxel micelles,
pharmacokinetics
POSTER SESSION 2 – P2.03A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
CLINICAL TRIALS –
TUESDAY, DECEMBER 6, 2016
P2.03A-053 IMMUNO-INFLAMMATORY MARKERS IN ADVANCED
NSCLC PATIENTS UNDERGONE FRACTIONED CISPLATIN, ORAL
ETOPOSIDE AND BEVACIZUMAB
Pierpaolo Pastina 1 , Valerio Nardone 1 , Battaglia Giuseppe 1 , Cirino Botta 2 ,
Paolo Tini 1 , Cristiana Bellan 1 , Veronica Ricci 1 , Marcella Barbarino 1 , Stefania
Croci 1 , Michele Caraglia 3 , Antonio Giordano 1 , Maria Grazia Cusi 1 , Luigi Pirtoli 1 ,
Pierpaolo Correale 1
1 Azienda Ospedaliera Universitaria Senese, Siena/Italy, 2 Magna Graecia University
of Catanzaro, Catanzaro/Italy, 3 Second University of Naples, Napoli/Italy
Background: The BEVA2007 study is a multistep phase I-II trial aimed to
investigate in advanced NSCLC patients the safety, the immunobiological
and the antitumor activity of the mPEBev, an original metronomic chemobiological
regimen whose results showed significant antiangiogenic and
immune-modulating and antitumor activity. Methods: Eighty-six advanced
NSCLC patients (76 males and 10 females; 53, adenocarcinoma; 13 squamous
carcinoma; and 20 with different subtypes) were enrolled between September
2007 and September 2015. All of them received cisplatin (30mg/sqm, days
1-3q21), oral etoposide (50mg, days 1-15q21) and bevacizumab 5mg/kg on
the day 3q21 (mPEBev regimen). Results: There were two cases of fatal
bleeding after 3 and 4 treatment courses, and five cases of severe infections
fully recovered with medical treatment. Hematological toxicity [grade 1-3
leukopenia (25%), anemia (25%)], g 1-2 gastroenteric toxicity (10%) and
alopecia (50%) were the most common adverse events. There was a partial
response in 54 cases ( 62,8%) and a stable disease in 9 cases (10,5%) with
a mean progression free survival (PFS) and overall survival (OS) of 13.46
(8.39-18.54) and 20.57 (14.5-26.6) months, respectively. Log-rank tests,
revealed a longer survival in patients with baseline levels of Neutrofil to
lymphocyte ratio (NLR) [L vs. H= 24.9 vs. 8.9 months, P=0.033], IL17 [L vs. H=
32.9 vs 11 months, P=0.033], leptine [L vs. H= 30,5 vs 8,5 months, P=0,025]
and T reg
s [L vs. H= 35.37 vs 9.9 months, P=0.049] lower than median value of
each specific parameter. A longer survival was also found in patients with a
treatment related fold increase to baseline > 1 in CD4+/CD8+ t cell ratio and
DCs expressing CD83 [L vs H 8.4 vs 20.85 months, P=0.05 ] and CD80 [L vs H = 8
vs 23 months, P=0.046]. Conclusion: These results suggest that both systemic
Inflammatory status and treatment-related immunomodulation may affect
the outcome of these patients a finding that highlight a possible involvement
of immunesystem in ultimate antitumor effect of this regimen, and offer
a solid rationale to test our metronomic regimen in a module of sequential
combination with anti-PD-1/PDL-1 inhibitors.
Keywords: chemoimmunotherapy, nsclc, Immuno-inflammatry, markers
POSTER SESSION 2 – P2.03A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
CLINICAL TRIALS –
TUESDAY, DECEMBER 6, 2016
P2.03A-054 A SINGLE-ARM PHASE II STUDY OF NAB-PACLITAXEL
FOR PATIENTS WITH CHEMOREFRACTORY NON-SMALL CELL LUNG
CANCER
Hisashi Tanaka 1 , Kageaki Taima 1 , Takeshi Morimoto 1 , Yoshihito Tanaka 1 ,
Masamichi Itoga 1 , Kunihiko Nakamura 2 , Akihito Hayashi 2 , Mika Kumagai 2 ,
Hideo Yasugahira 2 , Megumi Mikuniya 3 , Koichi Okudera 3 , Shingo Takanashi 4 ,
Sadatomo Tasaka 1
1 Department of Respiratory Medicine, Hirosaki University, Hirosaki/Japan,
2 Department of Respiratory Medicine, Hachinohe City Hospital, Hachinohe/Japan,
3 Hirosaki Chuo Hospital, Hirosaki/Japan, 4 Health Administration Center, Hirosaki
University, Hirosaki/Japan
Background: Background: Albumin-bound paclitaxel (nab-PTX) is a paclitaxel
formulation in which nanoparticles of PTX are bound to human serum
albumin. We conducted this study to evaluate the efficacy and safety of nab-
PTX in patients with advanced non-small cell lung cancer (NSCLC) who failed
previous chemotherapy. Methods: Methods: Eligible patients had refractory
advanced NSCLC. Patients were required to have an Eastern Cooperative
Copyright © 2016 by the International Association for the Study of Lung Cancer
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