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W. Park
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-092 - Central Nervous System (CNS) Responses to Osimertinib in Brain Metastases from Lung Cancer (NSCLC) with T790M: Effectiveness of the 80 Mg Dose (ID 4403)
14:30 - 14:30 | Author(s): W. Park
- Abstract
Background:
Patients with progressive CNS metastases from NSCLC who fail radiation therapy (RT) have a poor prognosis and short survival. Systemic chemotherapy is not very effective in controlling CNS metastases that failed RT. Patients with EGFR mutated NSCLC have a higher incidence of CNS metastases on presentation, and during the course of their illness. First and second generation tyrosine kinase inhibitors (TKI) at standard or pulse doses, may produce some clinically significant responses in the brain. Osimertinib is a potent irreversible EGFR TKI selective for activating EGFR and T790M resistance mutations. It has improved CNS penetration compared to older generations TKI. Previous reports have demonstrated the activity of osimertinib in the CNS at 160 mg. We report two patients who had failed RT treatment in the brain, who responded very well to the standard dose of osimertinib at 80 mg.
Methods:
Retrospective review of the charts of two patients was performed.
Results:
A 41-year old man diagnosed with metastatic adenocarcinoma of the lung with bilateral pulmonary nodules and 3 small brain micro metastases in April 2014. His lung biopsy revealed an EGFR Del 19. He was treated with cyberknife to the brain and Afatinib/Bevacizumab with an excellent response that lasted 11 months. Progressive brain metastases developed in May 2015 and treated with whole brain RT (WBRT). Lumbar puncture was negative for leptomeningeal disease. He was continued on Afatinib/Bevacizumab until November 2015, when he progressed in the lungs and the brain. Repeat lung biopsy revealed an EGFR T790M. He was not a candidate for additional RT. He was started on osimertinib at 80 mg in December 2015. Two months later, brain MRI revealed near complete resolution of the lesions, PET scan showed a significant response. Five months later, brain MRI remains negative and he remains in near complete systemic remission. An 84-year old female was diagnosed with multiple brain lesions in January 2015. Work up revealed a right lung mass, biopsy showed adenocarcinoma. She received WBRT. Blood-based cell-free DNA assay (Guardant 360) revealed an EGFR Del 19. She was treated with Erlotinib for 4 months and developed progression in the lungs. Repeat Guardant 360 revealed an EGFR T790M. Osimertinib 80 mg was started. She remains alive at 18 months with an excellent response in the brain .
Conclusion:
These two cases highlight the significant activity of osimertinib in the CNS at the standard 80 mg dose. Prospective studies should confirm this finding.
