Virtual Library
Start Your Search
Wei Zhang
Author of
-
+
EP1.03 - Biology (ID 193)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
-
+
EP1.03-11 - Mechanisms of Gefitinib Plus Pemetrexed on Human Non-Small Cell Lung Cancer (Now Available) (ID 1402)
08:00 - 18:00 | Author(s): Wei Zhang
- Abstract
Background
Resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI) is often acquired in non-small cell lung cancer (NSCLC) patients during treatment. We previously demonstrated that combined treatment with EGFR-TKI gefitinib plus chemotherapy improved progression-free survival (PFS) in NSCLC patients carrying sensitive EGFR mutations.
Method
Pharmacological interaction between gefitinib and pemetrexed was evaluated in NSCLC cell line PC-9 using MTT assay. The influence of combined treatment with gefitinib plus pemetrexed on gene expression profiles and signaling pathways has been investigated using microarray and Ingenuity Pathway Analysis (IPA).
Result
Synergistic inhibitory effect between gefitinib and pemetrexed was observed in NSCLC cell line PC-9. Figure 1A suggested representative proliferation inhibitory effects of gefitinib, pemetrexed and combined treatment for 48 hours. Figure 1B showed CI values of concurrent gefitinib-pemetrexed treatment in PC-9 NSCLC cell line. CI values at ED50, ED75 and ED90 were shown.
Furthermore, widespread gene expression changes and critical signaling pathways were induced significantly by combined treatment in PC-9 cells. Figure 2A was heatmap of gene expression prolifes in human NSCLC PC-9 cell line treated with gefitinib (blue), pemetrexed (purple) or gefitinib-pemetrexed combination (orange) with the criteria P<0.05 and ▏fold change ▏>1.5. Genes and samples were listed in rows and columns, respectively. A colour standard for data normalization was shown at the bottom with green representing downregulated genes while red representing upregulated genes. In Figure 2B, pathway enrichment of differential expressed genes was analysed using Ingenuity Pathway Analysis (IPA). Signaling pathways shown here were based on a P<0.0001. Figure 2C showed heatmap of critical pathways affected by combined treatment as compared to gefitinib single treatment. Heatmap colour represented the Z-score of signalling pathways. Z-score>0 meant the signalling pathway was stimulated by related treatment while Z-score<0 meant the signalling pathway was inhibited by related treatment.
Conclusion
Gene expression profiles revealed potential signaling pathways contributing to the synergism.
-
+
JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Track:
- Presentations: 1
- Moderators:Chunxue Bai, Tony Mok, Yi-Long Wu, Qing Zhou, Nan Wu
- Coordinates: 9/07/2019, 07:00 - 11:15, Toronto (1985)
-
+
JCSE01.20 - Pilot Study on the Tumor Immune Microenvironment Between Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) (ID 3434)
07:00 - 11:15 | Author(s): Wei Zhang
- Abstract
Abstract
Background
Tumor immune microenvironment plays an important role in immunotherapy and prognosis. However, the differences and the clinical significance between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) is still largely unknown.
Methods
Resected lung cancer FFPE specimens and matched peripheral blood mononuclear cells (PBMC) from six patients with NSCLC (three adenocarcinoma, three squamous cell carcinoma) and three patients with SCLC were collected. All of the nine patients underwent stage III disease. Tumor mutation burden (TMB) was evaluated by hybridization capture based next-generation sequencing with 1021 cancer associated genes. Tumor infiltrating lymphocytes (TILs) were assessed by immunohistochemistry using multiple immune markers and meanwhile the intratumoral T-cell repertoires were analyzed via high-throughput sequencing of TCR β-chain.
Results
Typical EGFR mutations in adenocarcinoma (2 in 3), NSCLC and RB1 mutations in SCLC (3 in 3) were observed. SCLC patients showed significantly higher TMB than NSCLC. Regarding to the tumor immune microenviroment, SCLC tumors exhibited lower infiltration of CD3+ and CD8+ TILs (P< 0.05). Furthermore, we found that SCLC patients tended to have lower TCR Shannon index (P= 0.167) and higher Clonality index (P= 0.095). Interestingly, patients with higher Shannon index exhibited better Overall Survival (OS) while Clonality was potentially associated with decreased OS. However, further study with more patients is needed to confirm the results.
Conclusion
Tumor immune microenvironment varies between NSCLC and SCLC patients. Specifically, less prevalent and lower diversity of TILs were observed in SCLCs. This might potentially influence survival outcomes.
-
+
MA25 - Precision Medicine in Advanced NSCLC (ID 352)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Sebastian Defranchi, Karen Kelly
- Coordinates: 9/10/2019, 14:30 - 16:00, Dublin (1997)
-
+
MA25.09 - Navigating Anlotinib Precision Therapy Through the Genetic Profiling of Circulating DNA in Non-Small Cell Lung Cancer Patients (Now Available) (ID 1055)
14:30 - 16:00 | Author(s): Wei Zhang
- Abstract
- Presentation
Background
Anlotinib is an oral multi-targeted anti-angiogenic drug, and its clinical predictor for non-small cell lung cancer (NSCLC) patients is still elusive. The aim of this study is to screen predictor for anlotinib via non-invasive genetic profiling of plasma cell free DNA and circulating tumor DNA (cfDNA & ctDNA).
Method
Tumor-specific target capture to profile the circulating DNA of ALTER0303 (Evaluating NSCLC clinical anti-tumor efficacy through anlotinib therapy) study participants. Acquired mutations were screened out via comparing genetic profiling between baseline (BL) and progression disease (PD), and were used for anlotinib stratification. Based on the sequencing data at BL, tumor mutation index (TMI) was established from three independent predictors germline and somatic mutation burden (G+S MB), nonsynonymous and synonymous mutation burden (N+S MB) and unfavorable mutation score (UMS), and was used for predicting anlotinib responders. In addition, TMI combined with IDH1Exon4 mutation status also be examined for serving as predictor for anlotinib stratification.
Result
Our data firstly indicated no benefit (NB, PFS ≤ 45 days) patients can be mainly excluded via analysis of ARID1A and BRCA2 genetic profiling. Secondly, for the no durable benefit (NDB, 45 days < PFS ≤ 130 days) and durable clinical benefit (DCB, PFS > 130 days) patients, harboring lower mutation burden (G+S MB, N+S MB, and UMS) received more benefit from anlotinib therapy. Subsequently, we found the predictor-TMI can predict anlotinib responders upon discovery cohort (Median PFS: 210 days vs 126 days; p = 0.0238; AUC = 0.77), and validation cohort (Median PFS: 210 days vs 127 days; p = 0.0352) and all patients (Median PFS: 210 days vs 127 days; p = 0.0044) more effectively. Furthermore, the IDH1Exon4 mutation was identified as an unfavorable factor to anlotinib therapy under TMI-based stratification. Lastly, the TMI plus IDH1Exon4 mutation status predict response to anlotinib significantly (Median PFS: 210 days vs 127 days, p < 0.0001, AUC = 0.90; Median OS: 423 days vs 162 days, p < 0.0001, AUC = 0.80).
Conclusion
This study provides circulating DNA sequencing-based stratification for underlying anlotinib responders via non-invasive approach, and thus potentially improve clinical outcome for NSCLC patients at 3rd line.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
OA11 - Decomplexifying Molecular Targets, Immunotherapy and Treatment Settings in the Real World (ID 137)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:Kumar Prabhash, Jyoti D Patel
- Coordinates: 9/09/2019, 14:00 - 15:30, Interlaken (1988)
-
+
OA11.07 - Chemotherapy Plus EGFR-TKI as First-Line Treatment Provides Better Survival for EGFR Mutation NSCLC Patients: Update Data for NCT02148380 (Now Available) (ID 2207)
14:00 - 15:30 | Presenting Author(s): Wei Zhang
- Abstract
- Presentation
Background
Previously, we did a prospective study to compare pemetrexed plus carboplatin and gefitinib to either pemetrexed plus carboplatin or gefitinib alone as first-line therapy for lung adenocarcinoma patients harboring sensitive EGFR mutations (NCT02148380). The primary endpoint PFS was met at Oct 1, 2016. However, the OS of combinational group was not mature then [Han B, et al. Int J Cancer. 2017;141:1249-1256]. In the present study, we continued the OS follow-up until Sep 28 2018.
Method
The survival curves for OS were estimated with the Kaplan-Meier method and were compared between combination and gefitinib groups using the log-rank test. 2-years, 3-years survival rates were compared between combination and gefitinib groups using Pearson Chi-Square.
Result
Baseline characteristics of the intent-to-treat (ITT) population have been reported. At last day of follow-up (Sep 28 2018), 30 (75.0%) patients in the combinational group, 35 (85.4%) patients in the gefitinib group died. 2-year survival rates of combinational and gefitinib groups were 85.0% (34/40), 56.1% (23/41) (P=0.004), respectively. 3-year survival rates of combinational and gefitinib groups were 52.5% (21/40), 24.4% (10/41) (P=0.009), respectively. The median OS was 37.9 months (95%CI: 17.3-58.6) for the combinational group, which was substantially longer than the median OS for first-line gefitinib group (25.8 months [95%CI: 19.2-32.3]). The HR of combinational group versus gefitinib group was 0.56 (95%CI:0.34-0.91, P=0.02).
19del: The median OS was 51.0 months (95%CI: 36.6-65.5) for the combinational group, which was substantially longer than the median OS for first-line gefitinib group (29.8 months [95%CI: 26.7-32.9]). The HR of combinational group versus gefitinib group was 0.61 (95%CI:0.30-1.25, P=0.18).
21L858R: The median OS was 32.3 months (95%CI: 27.8-36.7) for the combinational group, which was substantially longer than the median OS for first-line gefitinib group (22.8 months [95%CI: 13.1-32.5]). The HR of combinational group versus gefitinib group was 0.50 (95%CI:0.25-1.00, P=0.05).
Totally, 15 patients had baseline central nervous system (CNS) metastases. The median OS of patients who had baseline CNS metastases was 25.6 months (95%CI: 15.1-36.1); the median OS of patients who had no baseline CNS metastases was 31.7 months (95%CI: 28.2-35.2). The HR of CNS metastases group versus no CNS metastases group was 2.80 (95%CI:1.51-5.18, P=0.001). Among the combinational group, 20% (8/40) percent of patients had baseline CNS metastases. 17.1% (7/41) percent of patients in the gefitinib group had baseline CNS metastases.
CNS: The median OS was 27.0 months, (95%CI: 21.8-32.3) for the combinational group, which was substantially longer than the median OS for first-line gefitinib group (15.5 months, 95%CI: 6.8-24.3). The HR of combinational group versus gefitinib group was 0.17 (95%CI:0.04-0.68, P=0.013).
No CNS: The median OS was 47.4 months, 95%CI: 27.2-67.7 for the combinational group, which was substantially longer than the median OS for first-line gefitinib group (27.4 months, 95%CI: 23.0-33.7). The HR of combinational group versus gefitinib group was 0.57 (95%CI:0.32-0.99, P=0.044).
Conclusion
The current study on lung adenocarcinoma patients harboring sensitive EGFR mutations showed that the combined treatment with pemetrexed plus carboplatin with gefitinib provide better survival benefits than gefitinib alone.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.01-95 - Efficacy and Safety of Anlotinib in Combination with Chemotherapy as First-Line Therapy in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 2296)
09:45 - 18:00 | Author(s): Wei Zhang
- Abstract
Background
Anlotinib (AL3818) is a novel multi-target angioenesis TKI targeting the VEGFR, FGFR, PDGFR and c-Kit. In the ALTER0303 trial, Anlotinib as third-line treatment significantly improved progress-free survival (PFS) and overall survival (OS) in advanced NSCLC patients. This is the first trial evaluating the combination of chemotherapy and anlotinib in treatment-naive advanced NSCLC and is one arm of Phase II anlotinib-based trial (NCT03628521).
Method
Patients with previously untreated EGFR/ALK/ROS1 negative advanced NSCLC were enrolled. Eligible patients received anlotinib (12 mg QD from day 1 to 14 of a 21-day cycle) combined with carboplatin (AUC 5) and pemetrexed (adenocarcinoma, 500mg/m2)/gemcitabine (squamous, 1.0g/m2，day1&8) for four to six cycles (21-day cycle). Maintenance treatment was followed by using pemetrexed and anlotinib (anlotinib alone for squamous) until disease progression or treatment intolerance. The primary outcome was objective response (ORR) and secondary outcomes were PFS, disease control rate (DCR) and OS.
Result
Until the 21st March 2019, the curative effect was assessed in 30 enrolled patients according to the RECIST 1.1. Among these patients, eighteen of them achieved PR (all confirmed), eleven of them achieved SD and only one patient developed to disease progression. The objective response rate was 60.0 % while the disease control rate was 96.7 %. The most common Grade 3 adverse events were decreased platelet count (20 %), hypertriglyceridemia (10 %) and oral mucositis (6.67 %). 3 patients showed Grade 4 decrease of platelet count (10 %), and both of them belong to the gemcitabine group.
Conclusion
The combination of anlotinib and chemotherapy showed the potential effect and a manageable safety profile in patients with previously untreated EGFR/ALK/ROS1 negative advanced NSCLC.
Table 1: Response rates
Response
Assessed
CR
0
PR
18/30（60.0%）
SD
11/30（36.7%）
PD
1/30 （3.3%）
ORR, n/N（%）
18/30 （60.0%）
DCR, n/N（%）
29/30 （96.7%）
-
+
P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.04-02 - Efficacy and Safety of Sintilimab with Anlotinib as First-Line Therapy for Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 939)
09:45 - 18:00 | Author(s): Wei Zhang
- Abstract
Background
Given the synergy effect of immunotherapy and anti-angiogenic therapy in advanced NSCLC, FDA approved atezolizumab plus bevacizumab and chemotherapy as first-line treatment. However, chemo-free first-line strategy of PD-1/PD-L1 inhibitor combining angiogenesis modulator remains to be explored. This is the first trial evaluating sintilimab (anti-PD-1) plus anlotinib (multi-target TKI against tumor angiogenesis and proliferation) in treatment-naive advanced NSCLC patients and is one arm of Phase I anlotinib-based trial (NCT03628521).
Method
Treatment-naive, stage IIIB/IV NSCLC patients aged 18-75 with ECOG PS 0-1 were eligible. Patients with EGFR, ALK or ROS1 mutations were excluded. Participants were given intravenous sintilimab (200mg q3w) and oral anlotinib (12mg/d 2 weeks on/1 week off) until progression or unacceptable toxicity. The primary endpoints were ORR and safety. The secondary endpoints included DCR, PFS and OS. AEs were graded according to CTCAE v4.0.
Result
From September-2018 to February-2019, 22 patients were enrolled. Most were male (95.5%), former/current smokers (63.6%) and squamous cell histology (54.5%). 4 had baseline brain metastases. All patients have received at least once tumor assessment as of Jul-3th-2019. Among all, 16 achieved confirmed PR, 6 achieved SD, ORR was 72.7% (49.8%, 89.3%) and DCR was 100% (84.6%, 100%). 6 month PFS rate is 93.8% (95%CI: 63.23%, 99.10%). Overall, sintilimab and anlotinib was well tolerated. 6 (27.3%) had grade 3 and above treatment related adverse event (TRAE). The most common TRAE included fecal occult blood, hyperuricemia, hyponatremia, foot-hand syndrome, etc. 21 patients had baseline PD-L1-evaluated and 18 patients got TMB status (details in table). Notably, 5 of 6 SD patients developed cavities inside, suggesting a synergetic anti-tumor effect from combination regimen.
Conclusion
In this interim analysis, sintilimab plus anlotinib showed high ORR (72.7%) and DCR (100%) with tolerable safety profile, supporting worthy of further development from this convenient chemo-free regimen in first line setting.
-
+
P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.01-21 - Efficacy and Safety of Combing Anlotinib and Erlotinib as a First-Line Therapy in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 2361)
10:15 - 18:15 | Author(s): Wei Zhang
- Abstract
Background
As a promising multi-target tyrosine kinase inhibitor (TKI), anlotinib hydrochloride significantly improved overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients in the phase 3 trial ALTER0303. Antiangiogenesis therapy combined with EGFR-TKI has shown excellent efficacy and survival benefits in patients with EGFR mutations. This is the first trial evaluating anlotinib plus erlotinib in treatment-naive advanced NSCLC patients and is one arm of Phase II anlotinib-based trial (NCT03628521).
Method
Patients with previously untreated, EGFR mutation–positive (exon 19 deletion or L858R) advanced NSCLC were enrolled. Eligible patients received anlotinib (10 mg QD from day 1 to 14 of a 21-day cycle) combined with erlotinib (at a dose of 150 mg once daily) until disease progression or treatment intolerance. The primary outcome was objective response (ORR) and secondary outcomes were PFS, disease control rate (DCR) and OS.
Result
Until the 21st March 2019, 26 patients were enrolled. All are under treatment and 17 have received at least one tumor assessment. Among these patients, fifteen of them achieved PR (9 confirmed, the rest waiting for next assessment), two of them achieved SD and no patient developed to disease progression. The objective response rate was 88.2 % while the disease control rate was 100 %.The most common Grade 3 TRAE were rash (15.38 %), oral mucositis (11.54%) and albuminuria (7.69 %), and no grade 4/5 observation.
Conclusion
The combination of anlotinib and erlotinib showed the promising efficacy for previously untreated, EGFR mutation–positive advanced NSCLC patients with a manageable safety profile.
Table 1: Response rates
Response
Assessed
CR
0
PR
15/17（88.2%）
SD
2/17（11.76%）
PD
0
ORR, n/N（%）
15/17 (88.2%)
DCR, n/N（%）
17/17 (100.0%)
-
+
P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.03-49 - Roles of CENPU in Lung Adenocarcinoma Progression and Invasion (Now Available) (ID 1382)
10:15 - 18:15 | Author(s): Wei Zhang
- Abstract
Background
Centromere protein U (CENPU), a centromere protein mediating kinetochore-microtubule interaction, is critical for proper cell cycle and mitosis. It has been implicated that CENPU promotes tumorigenesis in variant malignancies. However, roles of CENPU in lung adenocarcinoma progression and underlying mechanisms remain to be elucidated.
Method
CENPU expression in 90 pair lung adenocarcinoma/adjacent normal lung samples was examined with immunohistochemistry (IHC). Then CENPU expression was inhibited with lentiviral-mediated shRNA strategy in human lung adenocarcinoma cell line H1299 to examine the impact of CENPU knockdown for lung adenocarcinoma progression and metastasis. Cell proliferation, colony formation, cell cycle and cell survival were analyzed by Cellomics cell counting method, colonogenesis assay, PI and Annexin V-APC staining respectively while cellular migration and invasion were determined by cell scratch and transwell test. Furthermore, expression of critical factors involved in epithelial-to-mesenchymal transition (EMT) were determined with western blot.
Result
CENPU expression was significantly increased in lung adenocarcinomas as compared to adjacent normal lung tissues (fold change=8.54, P<0.0001) (Fig. 1A). Functionl analysis revealed that in human lung adenocarcinoma cell line H1299, CENPU knockdown impaired cell proliferation (Fig. 1B), inhibited colony formation ability (Fig. 1C) and induced cell cycle arrest (Fig. 1D). Additionally, cellular migration and invasion was also inhibited by CENPU knockdown (Fig. 1E-F). It is further shown that E-Cadherin was induced while N-Cadherin and vimentin were inhibited by CENPU knockdown (Fig. 1G), indicating that CENPU was important for EMT process and cancer metastasis.
Conclusion
It showed that CENPU expression is significantly upregulated lung adenocarcinoma tissue. Functional analysis indicated that CENPU is critical for cell proliferation, survival, migration and metastasis in lung adenocarcinoma cell line H1299. CENPU represents a promising target for lung adenocarcinoma therapy.
