1. Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer (BLOSSOM).
- Author
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Park S, Baldry R, Jung HA, Sun JM, Lee SH, Ahn JS, Kim YJ, Lee Y, Kim DW, Kim SW, Lee KH, Lee WJ, Choi JW, Chong K, Lee JI, Gwon SH, Son NH, and Ahn MJ
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Adult, Aged, 80 and over, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents therapeutic use, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Protein Kinase Inhibitors pharmacokinetics, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Meningeal Carcinomatosis secondary, Meningeal Carcinomatosis drug therapy, Meningeal Carcinomatosis genetics, Meningeal Neoplasms secondary, Meningeal Neoplasms drug therapy, Meningeal Neoplasms genetics, Indoles, Pyrimidines, Acrylamides therapeutic use, Acrylamides pharmacokinetics, Acrylamides administration & dosage, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Aniline Compounds pharmacokinetics, Aniline Compounds therapeutic use, Aniline Compounds administration & dosage, Aniline Compounds adverse effects, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, ErbB Receptors genetics, ErbB Receptors antagonists & inhibitors, Mutation
- Abstract
Purpose: Leptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs., Materials and Methods: In this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6., Results: A total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set-T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2., Conclusion: The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status.
- Published
- 2024
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