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Eduard Teixidor
Author of
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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
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-49 - Targeting STAT3-Positive Reactive Astrocytes with Silibinin in the Therapeutic Landscape of Non-Small-Cell Lung Cancer with Brain Metastases (Now Available) (ID 1336)
10:15 - 18:15 | Author(s): Eduard Teixidor
- Abstract
Background
Silibinin is a bioactive flavonolignan extracted from milk thistle (Silybum marianum) and is a direct inhibitor of STAT3 – with high affinity to both the Src homology-2 domain and the DNA-binding domain of STAT3. Pre-clinical data indicate that blocking STAT3 signaling in reactive astrocytes, a major component of the brain metastasis microenvironment, can decrease the number and size of brain metastases (BM).
Method
We present data on all patients diagnosed with BM from non-small cell lung cancer (NSCLC) from the Cancer Register of the Hospital Universitari Dr. Josep Trueta during 2013–2017. Age, gender, histology, and treatment in patients were recorded. During this period, some patients received compassionate use of Legasil®, a commercially available silibinin-based nutraceutical, in addition to standard oncologic treatment. The data cut-off for survival analysis was 28th March 2019.
Result
We identified 221 patients with NSCLC and BM. Median age: 62 y (range: 32–88 y); male: 161 (72.9%). Synchronous BM were observed at the diagnosis of primary lung cancer in 133 (60.2%) patients. Differences in median overall survival (mOS) were detected by histology subtype: adenocarcinoma (66.1%)=4.6 m, squamous (17.6%)=1.8 m, not otherwise specified (16.3%)=2.2 m, p=0.000003. Treatment effects on mOS are summarized in Table 1. In the subgroup of patients that received brain radiotherapy in addition to systemic therapy for BM, differences were maintained between patients that received Legasil® (n=15) or not (n=64):28.5 months vs 6.3 months (p=0.000052).
Table 1 Treatment % mOS
(without)mOS
(with treatment)p-value Brain radiotherapy 53.8% 1.9 m 5.1 m < 0.000001 Systemic therapy 52% 1.6 m 6.9 m < 0.000001 Brain surgery 5% 3.2 m 15.5 m =0.000127 Silibinin supplementation 8.1% 3.5 m 22.8 m =0.000001
Our data indicate that silibinin supplementation could contribute to the control of BM in patients with NSCLC. Further evaluation of silibinin, or other STAT3 inhibitors, in clinical trials is warranted in this setting.