Dataset Information

Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study.

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.

SUBMITTER: Yang JCH

PROVIDER: S-EPMC7030895 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study.

Yang James C H JCH Kim Sang-We SW Kim Dong-Wan DW Lee Jong-Seok JS Cho Byoung Chul BC Ahn Jin-Seok JS Lee Dae H DH Kim Tae Min TM Goldman Jonathan W JW Natale Ronald B RB Brown Andrew P AP Collins Barbara B Chmielecki Juliann J Vishwanathan Karthick K Mendoza-Naranjo Ariadna A Ahn Myung-Ju MJ

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20191206 6

<h4>Purpose</h4>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.<h4>Patients and methods</h4>Patients with cytologically confirmed LM received osimertinib 160 mg once daily. Objectives were to assess confirmed objective r ...[more]

PMID: 31809241

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Project description:BackgroundLeptomeningeal metastasis (LM) is a catastrophic complication for patients with non-small cell lung cancer (NSCLC) and carries an extremely poor prognosis. The efficacy of osimertinib 80 mg once daily for epidermal growth factor receptor-mutated (EGFRm) NSCLC with LM has yet to be fully assessed. This study aimed to investigate the efficacy of osimertinib in such patients and their genetic profiles at the time of LM diagnosis.MethodsFrom January 2016 to April 2020, pretreated EGFRm NSCLC patients who had progressed with cytologically confirmed symptomatic LM and received osimertinib 80 mg once daily were enrolled retrospectively. The objective response rate (ORR) and disease control rate (DCR) were evaluated, along with progression-free survival (PFS) and overall survival (OS). Next-generation sequencing of paired samples of cerebrospinal fluid and plasma collected at LM diagnosis was performed simultaneously.ResultsForty cases of EGFRm lung adenocarcinoma with LM were analyzed. Females accounted for 75.0% of enrollees. Of the patients, 37.5% had a poor Eastern Cooperative Oncology Group score (≥2). Twelve patients had received at least 2 prior lines of treatment. All patients received osimertinib treatment regardless of their T790M status. According to the Response Assessment in Neuro-Oncology (RANO)-LM criteria, the ORR and DCR were 20.0% and 95.0%, respectively. The median PFS and OS were 10.0 (95% CI: 7.7-12.3) and 15.1 months (95% CI: 11.0-19.4), respectively. No significant difference was observed between T790M-negative patients (n=24) and T790M-positive patients (n=16) with respect to PFS [median, 10.8 (95% CI: 7.7-13.8) vs. 8.8 months (95% CI: 7.3-10.3), HR=0.595, P=0.158] or OS [median, 17.2 (95% CI: 8.7-25.7) vs. 11.4 months (95% CI: 3.9-19.0), HR=0.913, P=0.822]. The detection rate of EGFR sensitizing mutations in cerebrospinal fluid was higher than that in plasma (97.5% vs. 50%, P=0.311), whereas the incidence of T790M detection in cerebrospinal fluid was significantly lower than that in plasma (20.0% vs. 32.5%, P=0.043).ConclusionsOsimertinib 80 mg once daily shows good efficacy in pretreated EGFRm NSCLC patients with LM regardless of their T790M status. Combining cerebrospinal fluid and plasma testing can aid in revealing more genetic information.

Project description:BackgroundOsteoblastic bone reaction (OBR) refers to an increase in bone density at the site of bone metastasis or the appearance of new sclerotic bone lesions after anticancer treatment. OBR can be misunderstood as disease progression. In this study, we aimed to investigate the prevalence and details of OBR and its association with clinical outcomes in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with osimertinib.MethodsThis was a single-center, retrospective cohort study. We reviewed patients who were diagnosed with EGFR-mutant NSCLC with bone metastasis and received osimertinib as a first-line treatment between February 2018 and October 2022. The OBR was evaluated by comparing baseline computed tomography (CT) scans with the first CT scan after treatment initiation.ResultsA total of 45 patients were included in this study. Thirty-seven patients (82%) developed OBR. OBR developed in 94% (n = 16) of patients with sclerotic bone lesions (n = 17) at baseline. Similarly, OBR developed in lytic and mixed bone lesions in 76% and 82% of patients with lytic and mixed lesions, respectively. Progression-free survival (PFS) did not differ significantly between patients with (OBR group) and without OBR (non-OBR group) (median PFS, 24 months vs. 17 months; hazard ratio (HR), 0.62; 95% CI, 0.24-1.6; p = 0.31). In univariate analysis, the OBR group showed a trend toward longer skeletal-related events-free survival (SRE-FS) than the non-OBR group (median SRE-FS, 26 months vs. 12 months; HR, 0.53; 95% CI, 0.21-1.33; p = 0.16). Multivariate analysis showed OBR was a significant independent predictor of SRE-FS (HR, 0.35; 95% CI, 0.13-0.92; p = 0.034).ConclusionsOBR developed in most patients with NSCLC and bone metastasis who received osimertinib treatment. The increased incidence of OBR in patients with EGFR-mutant NSCLC with bone metastasis treated with osimertinib should not be confused with disease progression, and treatment decisions should be made carefully.

Dataset Information

Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study.

Purpose

Patients and methods

Results

Conclusion

Publications

Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study.

Similar Datasets

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