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Qiming Wang
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-017 - ALK-Rearranged May Promote VTE by Increasing the Expression of TF in Advanced Lung Adenocarcinoma (ID 9778)
09:30 - 09:30 | Presenting Author(s): Qiming Wang
- Abstract
Background:
Patients with lung cancer are at increased risk for venous thromboembolism (VTE).About 8% to 15% of patients with advanced none small-cell lung cancer(NSCLC) experience a VTE in the course of their disease. However, the incidences of VTE in different molecular subtypes of NSCLC are rarely reported though they have big differentiation in clinical feature and therapeutic effect.Tissue Factor (TF) expressed in many solid tumors could bind and activate coagulation factor FVII and trigger the downstream coagulation cascade leading to thrombin generation and clot formation.
Method:
Here we extracted retrospective data from electronic medical records at Henan Cancer Hospital in China between January 2015 and January 2016. Lung adenocarcinomas with ALK-rearranged, EGFR mutation and both negative were classified. The incidence rate of VTE after diagnosed with lung adenocarcinoma was calculated and analyzed. Then we randomly selected ALK-rearranged and ALK-rearranged negative lung adenocarcinoma tissues and detected TF expression in them with imunohistochemistry.
Result:
At a median follow-up of 19 months, 5.85% (30 in 513) patients with advanced lung adenocarcinoma experienced VTE. Patients with different molecular subtypes put up different rate of VTE (P=0.0021). Among them ALK-rearranged were more likely to experience VTE (6 in 29, 20.69%). EGFR and both negative had lower rate of VTE and had no big difference between them (11 in 218, 5.05%; 13 in 266, 4.89% respectively).The expression of TF performed similar feature. TF high expression in ALK-rearranged tissues is 41.67% (10 in 24) dramatically higher than that in ALK-rearranged negative tissues (11.54%, 3 in 26, P=0.0152).
Conclusion:
The rate of VTE in ALK-rearranged advanced lung adenocarcinoma cohorts was about 4 fold higher than that in EGFR mutation and both negative patients. ALK-rearranged may promote that by increasing TF expression. The mechanism warrants further research.
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P1.01-047 - Analysis of EGFR Mutation Status in CSF and Blood in Lung Adenocarcinoma Patients with EGFR Mutation and CNS Metastasis (ID 9717)
09:30 - 09:30 | Presenting Author(s): Qiming Wang
- Abstract
Background:
Patients with non-small cell lung cancer（NSCLC）harboring epidermal growth factor receptor (EGFR) mutations benefit a great deal from EGFR tyrosine kinase inhibitors(TKIs). However, most patients get recrudesced within one or two years, and many of them progressed in central nerve system（CNS）.Owing to the blood– brain barrier, detecting tumor-derived cell-free DNA (cfDNA) in the blood of brain metastasis tumor patients is challenging. Detecting tumor-specific mutations in cerebral spinal fluid (CSF) became an alternative method.
Method:
41 initial or progressed lung adenocarcinoma patients with EGFR mutation and CNS metastasis from Henan Cancer Hospital were included in this study. 41 patients were all detected EGFR mutation status in CSF with dropplet digital PCR (ddPCR) and 37 in 41 patients were detected EGFR mutation status in blood with the same method. Their clinical informations were also collected at the same time.
Result:
The rate of EGFR mutations in CSF （15/41，36.6%）were obviously lower than that in blood（24/37，64.9%）（P=0.013), especially in those with EGFR exon 19del mutation patients (7/18 vs 13/16, P = 0.017), without TKIs treated patients (3/13 vs 8/11,P = 0.038) and less than 60 years patients (10/25 vs 17/22, P = 0.010). In patients with CNS symptoms positive, the rate of EGFR mutations in CSF was higher than those negative (13/27 vs 2/14 , P=0.033). In patients with MRI indicating leptomeningeal metastasis, the rate of EGFR mutations in CSF was higher than those not indicating(8/11 vs 7/30 , P=0.003).Clinical characteristics, EGFR mutation status in CSF and plasma (n = 41)
Characteristic n(%) Gender Male 23 (56.1) Female 18 (43.9) Age ≥ 60 16 (39) < 60 25 (61) Smoking status Yes 12 (29.3) No 29 (70.7) Brain metastases (MRI) Only metastatic tumors 30 (73.2) With meningeal lesions 11 (26.8) Brain metastatic tumor number Single 10 (24.4) Multiple 31 (75.6) Neurological symptoms Positive 15 (36.6) Negtive 26 (63.4) Prior TKIs treat Yes 28 (68.3) No 13 (31.7) CSF EGFR mution 19 7 (17.1) 21 6 (14.6) Both 2 (4.9) Negtive 26 (63.4) Blood EGFR mution 19 13 (31.7) 21 10 (24.4) Both 1 (2.4) Negtive 13 (31.7)
Conclusion:
The EGFR mutations status in CSF is different from that in blood in patients with EGFR mutation and CNS metastasis. This warrants confirmation in larger cohorts and further more studies are needed to find out the internal mechanism. Detecting EGFR mutations status in both blood and CSF will be helpful to make individualized treatment.
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P1.15 - SCLC/Neuroendocrine Tumors (ID 701)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.15-006 - Enriched Environment and Anti-Depressants Enhance Platinum Chemosensitivity of Small Cell Lung Cancer (ID 7377)
09:30 - 09:30 | Presenting Author(s): Qiming Wang
- Abstract
Background:
Small cell lung cancer (SCLC) is one of the most lethal malignancies with rapid chemoresistance. Based on our previous study, enriched environment (EE) has a clear effect on improving the mental state of mice and can reduce chemoresistance caused by platinum regimens. In this study we investigated the complex links between benign mental stress (EE) and chemosensitivity of SCLC, and use anti-depressants to improve the mental state of mice to observe its impact on chemosensitivity to platinum regimens, and the underlying mechanism was explored.
Method:
The mental state of mice was evaluation by behavior tests include: elevated plus maze (EPM), open field experiment (OF), forced swimming (FS). Then, the mice were transplanted subcutaneously and treated with cisplatin, carboplatin and oxaliplatin. The tumor was analyzed by gene expression profiling and the differential genes were screened. The expression level of differential genes were examed by real-time PCR, and verified by western bolt and immunohistochemistry, respectively. And then ABCG2 blocker was used for chemosensitivity verification in vivo and in vitro.
Result:
EE significantly increased the movement on openarms in the EPM (35.24 sec V.S. 16.78 sec, P<0.01), increased the center area time in OF test (54.25 sec V.S. 35.24 sec, P<0.05), significantly increased the struggling time in the FS test (46.02 sec V.S. 25.81 sec, P<0.01). Antidepressants can also significantly improve the state of depression of mice, but can not achieve the effect of EE. For platinum chemosensitivity test, the antidepressant drugs (Diazepam, Quetiapine and Clomipramine) have no direct inhibition to tumor cells. A can significantly increased the sensitivity of chemotherapy in mice, but can not achieve the inhibitory effect of EE. Next we found the serum BDNF levels significantly decreased in EE mice. Similarly, antidepressants also significantly reduced serum BDNF levels in mice. Gene expression profiles showed that a variety of genes were downregulated mainly in ABC transporters and drug metabolic pathways by EE and antidepressants. The expression level of ABCB1, ABCC2, ABCG2, ABCC9, PPARa, DPYD, GST-P1 and GSTM1 in SCLC sample were examed by real-time PCR, and verified by western bolt and immunohistochemistry, respectively. ABCG2 expression in tumor of EE and antidepressants mice were even 3 fold higher than control (P<0.001). Nicardipine blocks ABCG2 expression can restore chemosensitivity to platinum based drugs (P<0.001).
Conclusion:
Antidepressants can partially mimic the chemotherapeutic effect of EE and we confirm that the mechanism is partially achieved by increasing BDNF and reducing the expression of ABCG2.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-087 - Impact Factor Analysis for Efficacy and Prognosis of Anlotinib in NSCLC as Third-Line Treatment: Data from Trial ALTER 0303 (ID 9129)
09:30 - 09:30 | Author(s): Qiming Wang
- Abstract
Background:
Anlotinib hydrochloride is a novel TKI targeting the VEGFR, FGFR, PDGFR and c-Kit. With the capability of inhibiting the tumor angiogenesis and tumor cell itself, anlotinib had showed significantly improvement in OS (9.63 vs. 6.30 months, HR=0.68, 95%CI 0.54-0.87, p=0.0018) and PFS (5.37 vs. 1.40 months, HR=0.26, 95%CI 0.21-0.33, p<0.0001) in ALTER 0303 study for refractory cancer, a randomized, double-blind, placebo-controlled Phase Ⅲ trial in China. Here, we report the main impact factors affecting the efficacy and prognosis of anlotinib based on the data from ALTER0303 to elucidate the most benefit population.
Method:
Analyzed data were collected from 294 patients that were enrolled in ALTER0303 trial and received anlotinib treatment between 4[th] March 2015 and 15[th] August 2016. The statistical analysis was conducted using SPSS19.0 software, in which the measuring and enumeration materials were described with Mean±SD and frequency/percentage respectively, Kaplan-Meier method was used for survival curves in survival analysis. Independent impact factors of OS and PFS were identified by univariate and multivariate analysis in Cox proportional hazards regression model (Significant level, α=0.05).
Result:
Several factors were discovered to be associated with the efficacy of Anlotinib treatment. The impact factors were presented in Tab1.Tab1. Impact factors for PFS and OS analyzed by Cox proportional hazards regression model Independent risk factor Independent protective factor PFS Ratio of granulocytes to lymphocytes at PD (HR=1.07, 95%CI 1.041-1.100, p<0.0001) Elevated ALP level (HR=1.553, 95%CI 1.142-2.112, p=0.005) Baseline sum of longest diameters of target lesions (HR=1.004, 95%CI 1.001-1.006, p=0.007) Elevated TSH level (HR= 0.555, 95%CI 0.422-0.730, p<0.0001) Hypercholesteremia (HR=0.720, 95%CI 0.534-0.971, p=0.031) Hypertension (HR=0.482, 95%CI 0.370-0.628, p<0.0001) Hand-foot skin reaction (HR=0.489, 95%CI 0.373- 0.643, p<0.0001) Elevated LDL level (HR=0.630, 95%CI 0.437-0.909, p=0.014) Age (HR=0.987, 95%CI 0.975-0.999, p=0.039) OS Ratio of granulocytes to lymphocytes at PD (HR=1.116, 95%CI 1.081-1.151, p<0.0001) Baseline sum of longest diameters of target lesions (HR=1.006, 95%CI 1.003-1.008, p<0.0001) ECOG PS≥2 at PD (HR=2.245, 95%CI 1.704- 3.508, p<0.0001) Elevated TSH level (HR=0.725, 95%CI 0.524- 1.005, p=0.053) Hypertriglyceridemia (HR=0.601, 95%CI 0.440-0.821, p<0.0001) Rash (HR=0.581, 95%CI 0.369-0.916, p=0.019) Female (HR=0.713, 95%CI 0.533-0.953, p=0.022)
Conclusion:
This analysis explored the possible impact factors of PFS and OS in Anlotinib treatment. Moreover, we provide real data for the prediction of Anlotinib efficacy and most benefit population through the baseline characteristics and variety of clinical index. However, further analysis in the larger scale study is still looking forward.
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-017 - Blood Samples NGS for Baseline Molecular Signature of Anotinib Treated Advanced NSCLC Patients in ALTER0303 Trial (ID 9670)
09:30 - 09:30 | Author(s): Qiming Wang
- Abstract
Background:
Anlotinib hydrochloride, an oral multi-target TKI targeting VEGFR, FGFR, PDGFR and c-Kit, have demonstrated noticeable effects for advanced NSCLC as 3[rd] line treatment in phase III trial (ALTER0303). Anlotinib significantly improved OS (9.63 vs. 6.30 months, p=0.0018, HR=0.68) and PFS (5.37 vs 1.40 months, p<0.0001, HR=0.26) comparing to placebo. Here, we applied ctDNA-based NGS to investigate the association between baseline molecular signature and clinical parameters.
Method:
Blood samples were collected from patients who enrolled in Anlotinib arm in ALTER0303 trial. Total of 92 samples were analyzed by capture-based targeted ultra-deep sequencing using a panel consisting of critical exons and introns of 168 NSCLC-related genes for the baseline genetic profiling.
Result:
At baseline, ctDNA was detected in 85% samples (78/92), driver mutation was found in 58% (53/92) samples. POM121L12 and CDKN2A mutations showed a tendency of co-occurrence with TP53, and mutually exclusivity was found between KEAP1 and TP53. The correlation between baseline molecular signature and treatment efficacy measured by PFS or best response was also investigated. Maximum mutation allele frequency (MAF) at baseline was inversely correlated with PFS (P=0.006, HR=0.612, 95%CI: 0.402-0.932). Patients achieving SD or PR had a significantly lower MAF comparing to patients having PD as their best response (p=0.018). Tumor mutation burden (TMB) is positively correlated with age (p=0.016) and gender (p=0.01). POM121L12, TP53 and MYC statuses are correlated with metastases burden. Moreover, as an important drive gene, EGFR mutation and/or EGFR amplification was found in 36 patients at baseline. In 27 patients with sensitizing EGFR mutation (L858R or 19 del), no significant differences was found in PFS compare to those without this mutation (n=65) (5.53 vs 5.53 months, p=0.495, HR=1.16, 95%CI: 0.73-1.85). As well, no significant difference was found in PFS between the patients with (n=17) or without EGFR T790M mutation (5.53 vs 5.53 months, p=0.253, HR=1.35, 95%CI: 0.75-2.41). Interestingly, in patients with EGFR amplification (n=10), the PFS is significantly shorter than those with normal EGFR copy number (2.12 vs 5.57 months, p=0.002, HR=2.70, 95%CI: 0.99-7.36). However, a tendency of PFS benefit is still observed in patients with EGFR amplification treated by Anlotinib comparing placebo arm in ALTER0303 (1.40 months).
Conclusion:
According to available data, no correlation was found between PFS and EGFR sensitizing mutations or T790M in anlotinib treatment. The negative correlation of EGFR amplification and PFS is still need verification to eliminate the bias caused by the disparity and limitation of samples. A larger scale analysis is ongoing.
