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Y. Jiang
Author of
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-015 - Efficacy of the Irreversible ErbB Family Blocker Afatinib in Treatment of an Intracerebral Non-Small Cell Lung Cancer in Mice (ID 4965)
14:30 - 14:30 | Author(s): Y. Jiang
- Abstract
Background:
The prognosis of brain metastases (BM) from lung cancer is extremely poor. Some studies showed patients with BM responded well to afatinib, while little was known on detail mechanism. This study aimed to evaluate the efficacy of afatinib for BM and address whether it could actively penetrate brain-blood barrier (BBB) and hit its target.
Methods:
Tumor burden was evaluated weekly after administration of afatinib and vehicle, and pharmacokinetic and pharmacodynamics characteristics were measured in both normal mice and BM model mice.
Results:
Administration of 15mg/kg afatinib inhibited in vivo PC-9 tumor growth in brain with tumor growth inhibitory rate (TGI) of 79.8% and 90.2% on day 7 and 14, respectively. 30mg/kg afatinib exhibited the tumor regression on day 7 and 14 with TGI of 124.7% and 105%. The plasma concentration was 91.4±31.2 nM/L at 0.5h after afatinib administration, reached the peak (417.1±119.9 nM/L) at 1h, and still be detected at 24h. The CSF concentrations followed a similar pattern. A good correlation (R[2]=0.732) between plasma and CSF concentrations was demonstrated. Immunohistochemistry showed the signal of pEGFR was reduce by 90% at 1 hour after administration of 30mg/kg afatinib. A positive correlation between afatinib concentrations in CSF and pEGFR modulation was observed.
Conclusion:
Afatinib could penetrate into BBB contributing to brain tumor response. The exposure in CSF correlated with that in plasma, which was correlated with modulations of pEGFR in the tumor tissues. Our findings provide implication of potential application of afatinib in NSCLC patients with brain metastases.
