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Dongsheng Yue
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OA 16 - Treatment Strategies and Follow Up (ID 686)
- Event: WCLC 2017
- Type: Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:Jun Nakajima, T. Demmy
- Coordinates: 10/18/2017, 14:30 - 16:15, Room 315
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OA 16.04 - Efficacy and Safety of Erlotinib vs Vinorelbine/Cisplatin as Adjuvant Therapy for Stage IIIA EGFR Mutant NSCLC Patients (ID 8717)
14:30 - 16:15 | Presenting Author(s): Dongsheng Yue
- Abstract
- Presentation
Background:
Adjuvant chemotherapy remains the most important treatment for stage IIIA non-small cell lung cancer (NSCLC) after radical operation, but its benefits has reached plateau and high risk of recurrence. Previous studies SELECT and RADIANT have suggested a trend of improving DFS of erlotinib as adjuvant therapy for patients with activating mutations. This study is designed as prospective, open-label, randomized, multicenter phase II trial to investigate the efficacy and safety of erlotinib (E) as adjuvant therapy in comparison with vinorelbine/cisplatin (NP) chemotherapy in completely resected stage IIIA EGFR mutant patients.
Method:
Patients aged between 18 – 75 with ECOG PS 0–1, stage IIIA, EGFR-activating mutation (exon 19 or exon 21 L858R), reached R0 resection NSCLC were eligible. And patients were randomized(1:1) into either erlotinib (orally 150mg/day for 2 years, util relapse or unacceptable toxicity) or NP (vinorelbine 25mg/m[2] i.v. day 1, 8 and cisplatin 75mg/m[2] i.v. day 1, every 3 weeks for 4 cycles) group. Random assignment was stratified by EGFR mutation type (exon 19 vs exon 21), histology (adenocarcinoma vs non- ) and smoking status (smoker vs non-). The primary endpoint was 2-year disease free survival rate (DFSR), secondary endpoints include disease free survival (DFS), overall survival (OS), safety (NCI CTCAE 4.0) and quality of life (QoL), and exploratory biomarker analysis.
Result:
From Sep, 2012 to May, 2015, in total 102 patients from 16 centers across China were randomized to receive E (N=51) or NP (N=51). Median follow-up time was 33 months for E and 28 months for NP. Baseline characteristics of age, sex, PS, histology, smoking status, EGFR mutation subtypes were well balanced in each arm. Two-year DFSR was 81.35% (95%CI: 69.63-93.08) in E arm and 44.62% (95%CI: 26.86-62.38) in NP arm respectively (P<0.001) in ITT population. DFS was significantly prolonged with E vs NP (median, 42.41 vs 20.96 months, HR 0.271, 95% CI: 0.137-0.535; P<0.001). OS data from our trial are still immature. In current, the number of death events were 2 (E) and 13 (NP) arm. Safety profile was similar to previous studies of each agent in NSCLC, no new unexpected AE were observed in each arms.
Conclusion:
As compared with NP, E showed superior efficacy and should be considered therapeutic option for patients with R0 resected stage IIIA NSCLC with EGFR-activating mutation. (EVAN, NCT01683175).
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-004 - Long Non-Coding RNA XLOC_000090 Promotes Lung Cancer Migration Through Modulation of miR-4505 (ID 9285)
09:30 - 16:00 | Author(s): Dongsheng Yue
- Abstract
Background:
Many studies have shown that long non-coding RNAs (lncRNAs) are implicated in cancer progress including lung cancer. In our previous studies, we screened the differentially expressed lncRNAs between lung adenocarcinoma with lymph node metastasis and lung adenocarcinoma without lymph node metastasis by microarray analysis. XLOC_000090, an lncRNA without a known function, was identified. Here, we investigated the functions of XLOC_000090 in lung cancer.
Method:
The expression of XLOC_000090 was detected by qRT-PCR in 96 pairs of NSCLC tissues and the adjacent normal lung tissues. Then, we investigated the correlation between XLOC_000090 expression and clinicopathological variables and prognosis. Cell invasion and migration assay was used to detect cell invasion and migration ability in vitro. Murine model of lung cancer was used to detect the effect of XLOC_000090 on pulmonary metastasis in vivo. Dual luciferase reporter assay was used to determine the direct binding between XLOC_000090 and miR-4505.
Result:
Compared with normal lung tissues, XLOC_000090 expression was higher in NSCLC tissues (P<0.05). XLOC_000090 expression was associated with lymph node metastasis (P<0.05) and pathological stage (P<0.05). Patients with high XLOC_000090 expression exhibited significantly poorer disease-free survival and overall survival (P<0.05). XLOC_000090 overexpression increased tumor cell migration and invasion ability, whereas downregulation of XLOC_000090 expression decreased tumor cell migration and invasion ability in both A549 and Calu3 lung cancer cells. Murine model of lung cancer also showed that XLOC_000090 promoted metastasis of lung cancer cells in vivo. Furthermore, a potential XLOC_000090-targeting miRNA, miR-4505, was identified by ceRNA regulatory network prediction analysis. miR-4505 expression was significantly downregulated in lung cells transfected with XLOC_000090, and significantly upregulated in lung cells transfected with sh-XLOC_000090. Dual-luciferase reporter assay showed the direct binding between miR-4505 and XLOC_000090. XLOC_000090-promoted cell migration and invasion ability was diminished in miR-4505 overexpressed cells.
Conclusion:
Our results demonstrated that XLOC_000090 promoted the migration and invasion of lung cancer cells through regulating miR-4505. XLOC_000090 could be served as a new molecular marker for the progression and prognosis of patients with NSCLC.
