Abstract
ObjectivesCentral nervous system (CNS) metastases are very common in patients with non-small-cell lung cancer (NSCLC). We aimed to explore the clinical impact of osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), on CNS metastases in patients with advanced NSCLC in real-world setting.MethodsPatients with advanced NSCLC who received osimertinib after progression of early-generation EGFR-TKIs and CNS metastases on baseline brain scan were retrospectively collected. Primary outcomes were disease control rate (DCR) and progression-free survival (PFS), and secondary objectives were objective response rate (ORR), time to tumor response, median best percentage change from baseline in CNS target lesion (TL) size and safety.ResultsBetween Apr 1, 2017, and Dec 30, 2017, 22 patients met selection criteria, 15 with ≥ 1 measurable CNS lesion (RECIST 1.1) were included in CNS evaluable for response (cEFR) set. Among the 22 patients, ORR and DCR were 40.9% and 86.4%, respectively, with median PFS of 8.5 months (95% CI 4.1, 13.0). Median intracranial PFS was not reached. Of 15 patients in cEFR set, CNS DCR was 80.0% with complete response reported in 3 patients (20.0%). Median best percentage change from baseline in CNS TL size was − 40% (range − 100 to + 60%) and median time to CNS tumor response was 1.3 months. CNS ORR was 53.3%. The safety profile was acceptable and no new unexpected findings were found.ConclusionThis real-world analysis further confirmed that osimertinib indeed demonstrated clinically meaningful efficacy against CNS metastases in Chinese patients with advanced NSCLC.
Highlights
Central nervous system (CNS) metastases, such as leptomeningeal metastasis (LM) and brain metastasis (BM), are very common in non-small cell lung cancer (NSCLC) patients and are associated with a significant neurological deficit [1]
The other two patients were demonstrated to have no T790M mutation by plasma ctDNA analysis and cerebrospinal fluid (CSF) analysis, respectively, but received osimertinib after progression of gefitinib and erlotinib based on the presence of epidermal growth factor receptor (EGFR) exon21 L858R mutation
In this real-world study, 19 of 22 (86.4%) NSCLC patients with CNS metastasis and 12 of 15 (80.0%) CNS responseevaluable patients treated with osimertinib achieved a systemic and intracranial disease control, respectively, and the median progression-free survival (PFS) was 8.5 months
Summary
Central nervous system (CNS) metastases, such as leptomeningeal metastasis (LM) and brain metastasis (BM), are very common in non-small cell lung cancer (NSCLC) patients and are associated with a significant neurological deficit [1]. Treatment options for CNS metastases during or after first- or second-generation EGFR-TKIs include surgical resection, stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT) and chemotherapy, but with severe adverse effects or limited inability to cross the blood–brain barrier (BBB) [8,9,10,11]. These observations suggest that a drug with much better
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