J Clin Oncol 2019 Dec 06
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.
Related Questions
Do you consider using 160 mg osimertinib in patients with EGFR-positive metastatic NSCLC to the brain?
The BLOOM study [Yang et al., PMID 31809241] was the first to address the question of CNS dosage for patients with EGFR mutant NSCLC with brain metastases. In this, patients with cytologically confirmed leptomeningeal (LM) disease received osimertinib 160 mg once daily. LM disease was assessed by bl...
For patients with EGFR mutation positive NSCLC who progress on first line TKI without actionable resistance mechanisms, would you consider chemotherapy + targeted therapy as a second line option, or chemotherapy +/- immunotherapy?
Although the question assumes no actionable changes in the lung cancer, I do refer you to an excellent review of this topic, published last September (Piper-Vallillo et al., PMID 32552277), which included a table listing twenty-five open clinical trials for patients who have developed progression af...