Osimertinib Combined with Systemic Chemotherapy for EGFR Mutant, T790M-Negative, Non–Small Cell Lung Cancer Patients Who Develop Leptomeningeal Metastases with Extracranial Progression to Prior EGFR TKI
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Leptomeningeal metastasis (LM) is a rare but fatal clinical condition with a short survival time. The incidence of LM from epidermal growth factor receptor mutant (EGFRm) non–small cell lung cancer (NSCLC) has increased due to the limited efficacy of first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the central nervous system (CNS). Osimertinib is a third-generation, irreversible, CNS penetrant, oral EGFR TKI that demonstrates promising efficacy in CNS metastases regardless of T790M. Herein, we report four cases of T790M-negative EGFRm NSCLC patients treated with osimertinib combined with systemic chemotherapy, who progressed on prior EGFR TKI and developed LM with extracranial lesions. The combination treatment was well tolerated, and the mean overall survival from LM diagnosis was 14.7 months (95% confidence interval, 10.4 to 19.0). These results suggest that osimertinib combined with systemic chemotherapy would be a reasonable treatment option for T790M-negative EGFRm NSCLC patients who develop LM with extracranial progression to prior EGFR TKI. A further prospective study is warranted.
Abstract
Leptomeningeal metastasis (LM) is a rare but fatal clinical condition with a short survival time. The incidence of LM from epidermal growth factor receptor mutant (EGFRm) non–small cell lung cancer (NSCLC) has increased due to the limited efficacy of first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the central nervous system (CNS). Osimertinib is a third-generation, irreversible, CNS penetrant, oral EGFR TKI that demonstrates promising efficacy in CNS metastases regardless of T790M. Herein, we report four cases of T790M-negative EGFRm NSCLC patients treated with osimertinib combined with systemic chemotherapy, who progressed on prior EGFR TKI and developed LM with extracranial lesions. The combination treatment was well tolerated, and the mean overall survival from LM diagnosis was 14.7 months (95% confidence interval, 10.4 to 19.0). These results suggest that osimertinib combined with systemic chemotherapy would be a reasonable treatment option for T790M-negative EGFRm NSCLC patients who develop LM with extracranial progression to prior EGFR TKI. A further prospective study is warranted.
참고문헌 (15)
- Chamberlain MC, "Leptomeningeal metastasis", Curr Opin Oncol, 22, pp.627~635 (2010)
- Li YS, "Leptomeningeal metastases in patients with NSCLC with EGFR mutations", J Thorac Oncol, 11, pp.1962~1969 (2016)
- Kuiper JL, "Treatment and survival of patients with EGFR-mutated non-small cell lung cancer and leptomeningeal metastasis : a retrospective cohort analysis", Lung Cancer, 89, pp.255~261 (2015)
- Taillibert S, "Leptomeningeal metastasis", Handb Clin Neurol, 149, pp.169~204 (2018)
- Chamberlain M, "Leptomeningeal metastasis : a response assessment in neuro-oncology critical review of endpoints and response criteria of published randomized clinical trials", Neuro Oncol, 16, pp.1176~1185 (2014)
- Umemura S, "Clinical outcome in patients with leptomeningeal metastasis from non-small cell lung cancer : Okayama Lung Cancer Study Group", Lung Cancer, 77, pp.134~139 (2012)
- Lee E, "Erlotinib versus gefitinib for control of leptomeningeal carcinomatosis in non-small-cell lung cancer", J Thorac Oncol, 8, pp.1069~1074 (2013)
- Mok TS, "Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer", N Engl J Med, 376, pp.629~640 (2017)
- Yang JC, "Osimertinib in patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer and leptomeningeal metastases : the BLOOM study", J Clin Oncol, 38, pp.538~547 (2020)
- Ahn MJ, "Osimertinib for patients with leptomeningeal metastases associated with EGFR T790M-positive advanced NSCLC : the AURA leptomeningeal metastases analysis", J Thorac Oncol, 15, pp.637~648 (2020)
- Lee J, "Osimertinib improves overall survival in patients with EGFR-mutated NSCLC with leptomeningeal metastases regardless of T790M mutational status", J Thorac Oncol, 15, pp.1758~1766 (2020)
- Ballard P, "Preclinical comparison of osimertinib with other EGFR-TKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity", Clin Cancer Res, 22, pp.5130~5140 (2016)
- Lu ZQ, "Osimertinib combined with bevacizumab for leptomeningeal metastasis from EGFR-mutation non-small cell lung cancer : a phase II single-arm prospective clinical trial", Thorac Cancer, 12, pp.172~180 (2021)
- Yang Z, "AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastases", Sci Transl Med, 8, pp.368ra172~ (2016)
- Ahn MJ, "Activity and safety of AZD3759 in EGFR-mutant non-small-cell lung cancer with CNS metastases(BLOOM) : a phase 1, open-label, dose-escalation and dose-expansion study", Lancet Respir Med, 5, pp.891~902 (2017)