Afatinib helped overcome subsequent resistance to osimertinib in a patient with NSCLC having leptomeningeal metastasis baring acquired EGFR L718Q mutation: a case report.
BACKGROUND
The epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer has been successfully treated with tyrosine kinase inhibitors (TKIs). Acquired resistance becomes a tough issue when patients fail to respond to the third-generation TKI osimertinib. This study aimed to report a case baring acquired EGFR L858R/L718Q mutation in the central nervous system induced by osimertinib, which was successfully overcome using afatinib.


CASE PRESENTATION
A 65-year-old female patient was diagnosed with stage IV non-small-cell lung adenocarcinoma with synchronic brain metastasis in February 2015. Before and during treatment, 416 tumor-related genes were monitored dynamically by liquid biopsies using next-generation sequencing, and the treatment strategy was decided according to the gene status. At baseline, an EGFR L858R mutation in exon 21 was detected, so treatment with icotinib was started. After 8 months, she experienced disease progression with leptomeningeal metastasis and switched to osimertinib based on an acquired EGFR T790 M mutation. After 9 months, her disease progressed and an EGFR L718Q mutation was found in the cerebrospinal fluid. The patient was then challenged with afatinib, and her disease was under control for 4 months. In January 2017, the patient passed away, with an overall survival time of 23 months, 15 months after leptomeningeal metastasis.


CONCLUSION
The acquired EGFR L718Q mutation in the cerebrospinal fluid resulted in subsequent resistance to osimertinib and could be partly overcome using afatinib, indicating a promising treatment option in the clinic.
['Liu|Jing|J|', 'Jin|Bo|B|', 'Su|Hang|H|', 'Qu|Xiujuan|X|', 'Liu|Yunpeng|Y|http://orcid.org/0000-0002-9645-7990']
D000178:Acrylamides D000077716:Afatinib D000368:Aged D000814:Aniline Compounds D001932:Brain Neoplasms D002289:Carcinoma, Non-Small-Cell Lung D043844:Crown Ethers D018450:Disease Progression D019008:Drug Resistance, Neoplasm D066246:ErbB Receptors D017809:Fatal Outcome D005260:Female D005500:Follow-Up Studies D006801:Humans D008175:Lung Neoplasms D055756:Meningeal Carcinomatosis D009154:Mutation D047428:Protein Kinase Inhibitors D011799:Quinazolines
Afatinib NSCLC Leptomeningeal metastasis EGFR L718Q