CMET-24. NEXT-GENERATION EPIDERMAL GROWTH FACTOR RECEPTOR TYROSINE KINASE INHIBITORS FOR LEPTOMENINGEAL CARCINOMATOSIS

Abstract

EGFR mutation status is strongly correlated with leptomeningeal carcinomatosis in non-small-cell lung cancer. Historically, patients were treated with first-generation EGFR tyrosine kinase inhibitors, however most would eventually develop resistance and disease progression. Therefore, recent interest has sparked in investigating next-generation EGFR- TKI monotherapy. We report two patients treated with next-generation EGFR-TKI monotherapy, independent of whole brain radiotherapy, with favorable response and outcome. CASE 1: A 70-year-old woman with non-small cell lung adenocarcinoma in status post resection and erlotinib was in remission until 10 years later when she presented with findings of intracranial hypertension. Imaging demonstrated an enhancing right frontal lesion and leptomeningeal disease. After six months on afatinib 30 mg daily, she had near-complete resolution of symptoms and significant decrease in leptomeningeal enhancement. CASE 2: A 54-year-old woman with non-small-cell lung adenocarcinoma underwent resection and presented two years later with multifocal right frontotemporal hemorrhagic metastases and leptomeningeal enhancement. Pathology from brain tumor resection showed pulmonary adenocarcinoma with EGFR exon 19 mutation. She received a single pulsed dose of erlotinib 1500 mg followed by osimertinib 80 mg daily with significant improvement in symptoms and complete resolution on repeat neuroimaging two months later.

DISCUSSION

Systemic chemotherapy alone has traditionally been ineffective in patients with CNS metastasis, likely due to poor penetration of the blood brain barrier by early-generation EGFR-TKIs and evolving drug resistance. The next-generation EGFR-TKIs may have improved success in treatment of leptomeningeal metastases in non-small-cell lung adenocarcinoma when compared to the first- and second-generation EGFR-TKIs. This could be particularly true in patients with documented exon 19 deletions, as in our second case.

CONCLUSION

Next-generation EGFR-TKI monotherapy could be considered in select patients with leptomeningeal metastases from lung adenocarcinoma. More research is needed to review this potential therapeutic option, especially for use as first-line therapy.