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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).
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Aug 10; Vol. 42 (23), pp. 2747-2756. Date of Electronic Publication: 2024 Jun 03. - Publication Year :
- 2024
-
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.<br />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.<br />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.<br />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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 42
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 38828959
- Full Text :
- https://doi.org/10.1200/JCO.24.00708