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Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status.
J Thorac Oncol. 2020 Jul 09 [Online ahead of print]JT

Abstract

INTRODUCTION

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, efficiently penetrates the blood-brain barrier. This study explored whether treatment with osimertinib leads to improved overall survival (OS) for patients with EGFR-mutated NSCLC with leptomeningeal metastases (LM) compared with those not treated with osimertinib.

METHODS

From October 2008 to October 2019, patients with EGFR-mutated NSCLC and cytologically confirmed LM were retrospectively analyzed for OS according to osimertinib treatment and T790M mutational status. The OS was defined as the time from the diagnosis of LM to death.

RESULTS

For the 351 patients with LM included in the analysis, the median OS (mOS) was 8.1 months (95% confidence interval [CI]: 7.2-9.0). T790M mutation was detected in 88 of 197 patients tested, and a total of 110 patients were treated with osimertinib after LM. No difference in mOS according to T790M mutational status (10.1 mo [95% CI: 4.31-15.82] versus 9.0 [95% CI: 6.81-11.21], p = 0.936) was found. Nevertheless, patients treated with osimertinib had a superior OS of 17.0 months (95% CI: 15.13-18.94) compared with those not treated with osimertinib who had a mOS of 5.5 months (95% CI: 4.34-6.63), regardless of T790M mutational status (hazard ratio: 0.36 [95% CI: 0.28-0.47], p < 0.001). This was also considerably longer even than the mOS of 8.7 months (95% CI: 7.01-10.39) of those who were never treated with osimertinib but had first- or second-generation EGFR tyrosine kinase inhibitors.

CONCLUSIONS

Osimertinib is a promising treatment option for EGFR-mutated NSCLC with LM regardless of T790M mutational status.

Authors+Show Affiliations

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: silk.ahn@samsung.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32652216

Citation

Lee, Jiyun, et al. "Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status." Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer, 2020.
Lee J, Choi Y, Han J, et al. Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status. J Thorac Oncol. 2020.
Lee, J., Choi, Y., Han, J., Park, S., Jung, H. A., Su, J. M., Lee, S. H., Ahn, J. S., Park, K., & Ahn, M. J. (2020). Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer. https://doi.org/10.1016/j.jtho.2020.06.018
Lee J, et al. Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status. J Thorac Oncol. 2020 Jul 9; PubMed PMID: 32652216.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status. AU - Lee,Jiyun, AU - Choi,Yoon La, AU - Han,Joungho, AU - Park,Sehhoon, AU - Jung,Hyun Ae, AU - Su,Jong-Mu, AU - Lee,Se-Hoon, AU - Ahn,Jin Seok, AU - Park,Keunchil, AU - Ahn,Myung-Ju, Y1 - 2020/07/09/ PY - 2020/04/13/received PY - 2020/06/17/revised PY - 2020/06/19/accepted PY - 2020/7/12/pubmed PY - 2020/7/12/medline PY - 2020/7/12/entrez KW - Leptomeningeal metastases KW - NSCLC KW - Osimertinib KW - Overall survival KW - T790M JF - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JO - J Thorac Oncol N2 - INTRODUCTION: Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, efficiently penetrates the blood-brain barrier. This study explored whether treatment with osimertinib leads to improved overall survival (OS) for patients with EGFR-mutated NSCLC with leptomeningeal metastases (LM) compared with those not treated with osimertinib. METHODS: From October 2008 to October 2019, patients with EGFR-mutated NSCLC and cytologically confirmed LM were retrospectively analyzed for OS according to osimertinib treatment and T790M mutational status. The OS was defined as the time from the diagnosis of LM to death. RESULTS: For the 351 patients with LM included in the analysis, the median OS (mOS) was 8.1 months (95% confidence interval [CI]: 7.2-9.0). T790M mutation was detected in 88 of 197 patients tested, and a total of 110 patients were treated with osimertinib after LM. No difference in mOS according to T790M mutational status (10.1 mo [95% CI: 4.31-15.82] versus 9.0 [95% CI: 6.81-11.21], p = 0.936) was found. Nevertheless, patients treated with osimertinib had a superior OS of 17.0 months (95% CI: 15.13-18.94) compared with those not treated with osimertinib who had a mOS of 5.5 months (95% CI: 4.34-6.63), regardless of T790M mutational status (hazard ratio: 0.36 [95% CI: 0.28-0.47], p < 0.001). This was also considerably longer even than the mOS of 8.7 months (95% CI: 7.01-10.39) of those who were never treated with osimertinib but had first- or second-generation EGFR tyrosine kinase inhibitors. CONCLUSIONS: Osimertinib is a promising treatment option for EGFR-mutated NSCLC with LM regardless of T790M mutational status. SN - 1556-1380 UR - https://www.unboundmedicine.com/medline/citation/32652216/Osimertinib_improves_overall_survival_in_EGFR-mutated_non-small_cell_lung_cancer_patients_with_leptomeningeal_metastases_regardless_of_T790M_mutational_status L2 - https://linkinghub.elsevier.com/retrieve/pii/S1556-0864(20)30505-0 DB - PRIME DP - Unbound Medicine ER -
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