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E. Sais
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-035 - Efficacy of Nintedanib and Docetaxel in Combination with the Nutraceutical Use of Silibinin in Advanced NSCLC (ID 9511)
09:30 - 09:30 | Author(s): E. Sais
- Abstract
Background:
Nintedanib is an orally administered, small-molecule triple angiokinase inhibitor of VEGF1–3, PDGFa and b, and FGFR1–3. The LUME-Lung 1 trial showed that nintedanib significantly extended progression-free survival (PFS) and overall survival (OS) in patients with NSCLC adenocarcinoma when added to docetaxel chemotherapy. The bioactive flavonolignan silibinin, the main component of standardized extracts from the seeds of the milk thistle herb Silybum marianum, has been shown to exert significant anti-cancer effects in pre-clinical models. The oral use of the silibinin-containing nutraceutical Legasil[®] could represent the first silibinin formulation with proven clinical benefit as an adjunct cancer treatment.
Method:
Patients with stage IV NSCLC who failed ≥1 prior treatment were eligible for nintedanib/docetaxel combination. We present data of patients that received nintedanib plus docetaxel with or without combination with up to 5 capsules/day of Legasil[®], which equated to a 630 mg/ day dose silibinin regimen, as complementary treatment. The nature of the interaction between nintedanib and silibinin was explored in a broad panel of human NSCLC cell lines.
Result:
Twenty-two patients were enrolled in the study: median age 63y (range: 44–74); male: 14. All the cases were non-squamous NSCLC. All patients had received first line therapy; 3 patients had ≥2 prior lines of treatment. The mean PFS was 1.82 months (95% confidence interval [CI] 1.39–2.26) for the nintedanib plus docetaxel combination (n=7) versus 4.97 (95%CI 2.87–7.07) for the nintedanib, docetaxel and Legasil[® ]triple combination (n=15) (p=0.02). No statistically significant differences in mean OS were observed between the two arms: 4.88 (95%CI 3.26–6.48) for nintedanib plus docetaxel versus 10.3 (95%CI 5.85–14.76) for nintedanib plus docetaxel plus Legasil[® ](p=0.534). At the data cutoff in June 2017, 9 (41%) patients remained alive. A significant inverse correlation was found between nintedanib and silibinin sensitivity among NSCLC cell lines. The combined treatment of nintedanib and silibinin produced unanticipated, synergistic cytotoxic effects in nintedanib-unresponsive NSCLC cells.
Conclusion:
There is a clinical and biological rationale for combining nintedanib and docetaxel with the silibinin-containing nutraceutical Legasil[®] in patients with advanced NSCLC, where few effective second-line treatment options are available.
