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Afatinib helped overcome subsequent resistance to osimertinib in a patient with NSCLC having leptomeningeal metastasis baring acquired EGFR L718Q mutation: a case report.
BMC Cancer. 2019 Jul 17; 19(1):702.BC

Abstract

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.

Authors+Show Affiliations

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China. cmuquxiujuan@163.com. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China. cmuquxiujuan@163.com.Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China. ypliu@cmu.edu.cn. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China. ypliu@cmu.edu.cn.

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

31315676

Citation

Liu, Jing, et al. "Afatinib Helped Overcome Subsequent Resistance to Osimertinib in a Patient With NSCLC Having Leptomeningeal Metastasis Baring Acquired EGFR L718Q Mutation: a Case Report." BMC Cancer, vol. 19, no. 1, 2019, p. 702.
Liu J, Jin B, Su H, et al. Afatinib helped overcome subsequent resistance to osimertinib in a patient with NSCLC having leptomeningeal metastasis baring acquired EGFR L718Q mutation: a case report. BMC Cancer. 2019;19(1):702.
Liu, J., Jin, B., Su, H., Qu, X., & Liu, Y. (2019). Afatinib helped overcome subsequent resistance to osimertinib in a patient with NSCLC having leptomeningeal metastasis baring acquired EGFR L718Q mutation: a case report. BMC Cancer, 19(1), 702. https://doi.org/10.1186/s12885-019-5915-7
Liu J, et al. Afatinib Helped Overcome Subsequent Resistance to Osimertinib in a Patient With NSCLC Having Leptomeningeal Metastasis Baring Acquired EGFR L718Q Mutation: a Case Report. BMC Cancer. 2019 Jul 17;19(1):702. PubMed PMID: 31315676.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Afatinib helped overcome subsequent resistance to osimertinib in a patient with NSCLC having leptomeningeal metastasis baring acquired EGFR L718Q mutation: a case report. AU - Liu,Jing, AU - Jin,Bo, AU - Su,Hang, AU - Qu,Xiujuan, AU - Liu,Yunpeng, Y1 - 2019/07/17/ PY - 2019/04/03/received PY - 2019/07/09/accepted PY - 2019/7/19/entrez PY - 2019/7/19/pubmed PY - 2019/7/19/medline KW - Afatinib KW - EGFR KW - L718Q KW - Leptomeningeal metastasis KW - NSCLC SP - 702 EP - 702 JF - BMC cancer JO - BMC Cancer VL - 19 IS - 1 N2 - 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. SN - 1471-2407 UR - https://www.unboundmedicine.com/medline/citation/31315676/Afatinib_helped_overcome_subsequent_resistance_to_osimertinib_in_a_patient_with_NSCLC_having_leptomeningeal_metastasis_baring_acquired_EGFR_L718Q_mutation:_a_case_report_ L2 - https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5915-7 DB - PRIME DP - Unbound Medicine ER -