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Xueyan Zhang
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MA01 - Oligometastatic Disease (ID 114)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Now Available
- Moderators:Anne Marie Clasina Dingemans, Matthias Guckenberger
- Coordinates: 9/08/2019, 10:30 - 12:00, Copenhagen (1980)
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MA01.10 - Additional Local Consolidative Therapy Showed Survival Benefit Than EGFR-TKIs Alone in Bone Oligometastatic Lung Adenocarcinoma Patients (Now Available) (ID 398)
10:30 - 12:00 | Author(s): Xueyan Zhang
- Abstract
- Presentation
Background
Whether epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) plus local consolidative therapy (LCT) has better survival benefit than EGFR-TKIs alone remains controversial in lung adenocarcinoma patients with EGFR mutation and bone oligometastases.
Method
We conducted a retrospective study to assess the effects of LCT on bone oligometastases lung adenocarcinoma patients with EGFR mutation. The primary endpoint was overall survival (OS); The secondary endpoints was progression-free survival (PFS).
Result
A total of 127 lung adenocarcinoma patients with EGFR mutation and bone oligometastases were identified. There were 65 patients received EGFR-TKIs alone (monotherapy group) and 62 patients received EGFR-TKIs plus local consolidative therapy (LCT) (combination group). Addition of LCT was associated with a significantly longer OS (36.3 vs. 21.0 months, P=0.01, hazard ratio [HR]=0.537, 95% confidence interval [CI]:0.360-0.801, p=0.01) and PFS (14.0 vs. 8.1 months, P=0.01, HR=0.613, 95%CI: 0.427-0.879, p=0.01) in the whole cohort (Figure 1). All subgroups showed OS benefit in faver of combination therapy except for PS scores greater than or equal to 2 group, and all subgroups analyzed derived PFS benefit in favor of combination therapy (Figure 2).
Conclusion
In patients with EGFR-mutant lung adenocacinoma and bone oligometastases, LCT plus EGFR-TKIs therapy was associated with significantly longer OS and PFS than EGFR-TKIs therapy alone, indicating that LCT plus EGFR-TKIs therapy might be a better therapeutic option for those patient population.
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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
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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): Xueyan 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%）
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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
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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): Xueyan 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%)
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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
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P2.03-49 - Roles of CENPU in Lung Adenocarcinoma Progression and Invasion (Now Available) (ID 1382)
10:15 - 18:15 | Author(s): Xueyan 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.
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P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.16-26 - Opportunity of WBRT in EGFR-Mutated Lung Adenocarcinoma Patients with Multiple Brain Metastases: A Retrospective Study Based on DS-GPA (Now Available) (ID 1070)
10:15 - 18:15 | Author(s): Xueyan Zhang
- Abstract
Background
Whole-brain radiotherapy (WBRT) and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are effective treatment options for multiple brain metastases (BM) in patients with EGFR-mutant adenocarcinoma. This study evaluated the optimal treatment sequence between EGFR-TKI and WBRT in patients with EGFR mutation adenocarcinoma and multiple BM
Method
A total of 195 patients with EGFR-mutant adenocarcinoma with multiple BM were enrolled in the study. Patients were treated with EGFR-TKI for over 4 weeks after WBRT,received EGFR-TKI concurrently in phase with WBRT or within 4 weeks after WBRTor treated with WBRT during intracranial progression after EGFR-TKI initiation. Overall survival (OS) and disease-specific Graded Prognostic Assessment (DS-GPA) was measured.
Result
For the entire cohort, the median OS was 27 months (95% CI, 24.6 to 29.4). GPA-based subdivided patients : upfront WBRT of GPA, 0 to 1.5 (median: 30 months; n=36; 18%); upfront WBRT of GPA, 2.0 to 3.5 (median:48 months; n=31; 16%); EGFR-TKI concurrently with WBRT of GPA, 0 to 1.5 (median:20 months; n=38; 19%); EGFR-TKI concurrently with WBRT of GPA 2.0 to 3.5 (median:37 months; n=26; 13%); upfront EGFR-TKI of GPA 0 to 1.5 (median:26 months; n=45; 23%); and upfront EGFR-TKI of GPA, 2.0 to 3.5 (median:17 months; n=19; 10%).The prognosis of patients in different GPA groups differed significantly (p<0.0001). The data by these parameters and the results showed no imbalance with respect to the number of patients on GPA scores ( T=1.786，p=0.076).In groups at EGFR-TKI concurrently with WBRT and upfront EGFR-TKI, patients with GPA score 2-3.5 demonstrated a significantly longer OS than those at score 0-1.5 (P=0.023) , patients with EGFR-TKI concurrently with WBRT is longer than those with upfront EGFR-TKI in subgroup at GPA score 2-3.5(P=0.023).There was no difference in the OS at 0-1.5 score level between the EGFR-TKI concurrently with WBRT group and the upfront EGFR-TKI group (P=0.141).
Conclusion
For EGFR-mutated lung adenocarcinoma patients with multiple BM,the use of upfront WBRT achieved a significantly longer OS in high DS-GPA scores groups.
