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Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study.
J Clin Oncol. 2020 02 20; 38(6):538-547.JC

Abstract

PURPOSE

In this phase I study (BLOOM), osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was evaluated in patients with leptomeningeal metastases (LMs) from EGFR-mutated (EGFRm) advanced non-small-cell lung cancer (NSCLC) whose disease had progressed on previous EGFR-TKI therapy.

PATIENTS AND METHODS

Patients with cytologically confirmed LM received osimertinib 160 mg once daily. Objectives were to assess confirmed objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), pharmacokinetics (PK), and safety. Additional efficacy evaluations included changes from baseline in CSF cytology and neurologic examination. Measurable lesions were assessed by investigator according to RECIST version 1.1. LMs were assessed by neuroradiologic blinded central independent review (BICR) according to Response Assessment in Neuro-Oncology LM radiologic criteria and by investigator.

RESULTS

Forty-one patients were enrolled. LM ORR and DoR by neuroradiologic BICR were 62% (95% CI, 45% to 78%) and 15.2 months (95% CI, 7.5 to 17.5 months), respectively. Overall, ORR by investigator was 41% (95% CI, 26% to 58%), and median DoR was 8.3 months (95% CI, 5.6 to 16.5 months). Median investigator-assessed PFS was 8.6 months (95% CI, 5.4 to 13.7 months) with 78% maturity; median OS was 11.0 months (95% CI, 8.0 to 18.0 months) with 68% maturity. CSF tumor cell clearance was confirmed in 11 (28%; 95% CI, 15% to 44%) of 40 patients. Neurologic function was improved in 12 (57%) of 21 patients with an abnormal assessment at baseline. The adverse event and PK profiles were consistent with previous reports for osimertinib.

CONCLUSION

Osimertinib showed meaningful therapeutic efficacy in the CNS and a manageable safety profile at 160 mg once daily in patients with EGFRm NSCLC and LM.

Authors+Show Affiliations

National Taiwan University Hospital, Taipei, Republic of China.Asan Medical Center, Seoul, Republic of Korea.Seoul National University Hospital, Seoul, Republic of Korea.Seoul National University Bundang Hospital, Seongnam, Republic of Korea.Yonsei University College of Medicine, Seoul, Republic of Korea.Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Asan Medical Center, Seoul, Republic of Korea.Seoul National University Hospital, Seoul, Republic of Korea.University of California Los Angeles, Los Angeles, CA.Cedars-Sinai Medical Center, Los Angeles, CA.AstraZeneca, Cambridge, United Kingdom.AstraZeneca, Cambridge, United Kingdom.AstraZeneca, Waltham, MA.National Taiwan University Hospital, Taipei, Republic of China. AstraZeneca, Waltham, MA.AstraZeneca, Cambridge, United Kingdom.Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31809241

Citation

Yang, James C H., et al. "Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: the BLOOM Study." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 38, no. 6, 2020, pp. 538-547.
Yang JCH, Kim SW, Kim DW, et al. Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study. J Clin Oncol. 2020;38(6):538-547.
Yang, J. C. H., Kim, S. W., Kim, D. W., Lee, J. S., Cho, B. C., Ahn, J. S., Lee, D. H., Kim, T. M., Goldman, J. W., Natale, R. B., Brown, A. P., Collins, B., Chmielecki, J., Vishwanathan, K., Mendoza-Naranjo, A., & Ahn, M. J. (2020). Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 38(6), 538-547. https://doi.org/10.1200/JCO.19.00457
Yang JCH, et al. Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: the BLOOM Study. J Clin Oncol. 2020 02 20;38(6):538-547. PubMed PMID: 31809241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study. AU - Yang,James C H, AU - Kim,Sang-We, AU - Kim,Dong-Wan, AU - Lee,Jong-Seok, AU - Cho,Byoung Chul, AU - Ahn,Jin-Seok, AU - Lee,Dae H, AU - Kim,Tae Min, AU - Goldman,Jonathan W, AU - Natale,Ronald B, AU - Brown,Andrew P, AU - Collins,Barbara, AU - Chmielecki,Juliann, AU - Vishwanathan,Karthick, AU - Mendoza-Naranjo,Ariadna, AU - Ahn,Myung-Ju, Y1 - 2019/12/06/ PY - 2021/02/20/pmc-release PY - 2019/12/7/pubmed PY - 2020/8/29/medline PY - 2019/12/7/entrez SP - 538 EP - 547 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 38 IS - 6 N2 - PURPOSE: In this phase I study (BLOOM), osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was evaluated in patients with leptomeningeal metastases (LMs) from EGFR-mutated (EGFRm) advanced non-small-cell lung cancer (NSCLC) whose disease had progressed on previous EGFR-TKI therapy. PATIENTS AND METHODS: Patients with cytologically confirmed LM received osimertinib 160 mg once daily. Objectives were to assess confirmed objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), pharmacokinetics (PK), and safety. Additional efficacy evaluations included changes from baseline in CSF cytology and neurologic examination. Measurable lesions were assessed by investigator according to RECIST version 1.1. LMs were assessed by neuroradiologic blinded central independent review (BICR) according to Response Assessment in Neuro-Oncology LM radiologic criteria and by investigator. RESULTS: Forty-one patients were enrolled. LM ORR and DoR by neuroradiologic BICR were 62% (95% CI, 45% to 78%) and 15.2 months (95% CI, 7.5 to 17.5 months), respectively. Overall, ORR by investigator was 41% (95% CI, 26% to 58%), and median DoR was 8.3 months (95% CI, 5.6 to 16.5 months). Median investigator-assessed PFS was 8.6 months (95% CI, 5.4 to 13.7 months) with 78% maturity; median OS was 11.0 months (95% CI, 8.0 to 18.0 months) with 68% maturity. CSF tumor cell clearance was confirmed in 11 (28%; 95% CI, 15% to 44%) of 40 patients. Neurologic function was improved in 12 (57%) of 21 patients with an abnormal assessment at baseline. The adverse event and PK profiles were consistent with previous reports for osimertinib. CONCLUSION: Osimertinib showed meaningful therapeutic efficacy in the CNS and a manageable safety profile at 160 mg once daily in patients with EGFRm NSCLC and LM. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/31809241/Osimertinib_in_Patients_With_Epidermal_Growth_Factor_Receptor_Mutation_Positive_Non_Small_Cell_Lung_Cancer_and_Leptomeningeal_Metastases:_The_BLOOM_Study_ L2 - https://ascopubs.org/doi/10.1200/JCO.19.00457?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -