Osimertinib combined with bevacizumab for leptomeningeal metastasis from EGFR-mutation non-small cell lung cancer: A phase II single-arm prospective clinical trial.

BACKGROUND: Leptomeningeal metastasis (LM) is associated with poor prognosis in non-small cell lung cancer (NSCLC). The aim of this study was to investigate the efficacy and safety of osimertinib combined with bevacizumab for LM from epidermal growth factor receptor mutation (EGFRm) NSCLC. METHODS: We conducted a phase II single-arm prospective clinical trial of EGFRm NSCLC with LM treated with osimertinib combined with bevacizumab. LM response assessment was based on the modified RANO LM radiological criteria; CNS and extra-CNS response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary end points included LM progression-free survival (PFS) and objective response rate (ORR); the secondary end points included safety and LM overall survival (OS). RESULTS: A total of 14 patients were included in the study, with a median age of 61 years, and they were predominantly female (64%). EGFR mutations were reported in exons 19 del (n = 7) and 21 L858R (n = 7). When LM was diagnosed, 12 (85.7%) patients had clinical symptoms, 71.4% (10/14) of patients were diagnosed with LM by cytology, and five (35.7%) patients had a performance status (PS) score > 2. The median LM PFS was 9.3 months (95% CI: 8.2-10.4), and the LM ORR was 50%. The safety findings in the present study were consistent with the known profile of osimertinib with bevacizumab; the median LM OS was 12.6 months, and the one-year survival rate was 35.7%. CONCLUSIONS: Osimertinib combined with bevacizumab is an appropriate treatment option for patients with LM from EGFRm NSCLC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: To date, there is no prospective clinical study on the treatment of osimertinib combined with bevacizumab in EGFRm NSCLC with LM. WHAT THIS STUDY ADDS: The median LM PFS was 9.3 months (95% CI: 8.2-10.4), and the LM ORR was 50%, the median LM OS was 12.6 months, and the one-year survival rate was 35.7%. Osimertinib combined with bevacizumab is an appropriate treatment option for patients with LM from EGFRm NSCLC.

[Role of DNA-associated autoantibodies to cell membrane in the diagnosis of juvenile systemic lupus erythematosus].

OBJECTIVE: To establish a method of indirect immunofluorescence (IIF) to measure DNA (mDNA)-associated autoantibodies to cell membrane, and to evaluate diagnostic value of the anti-mDNA antibodies in patients with juvenile systemic lupus erythematosus (SLE) in comparison with anti-dsDNA antibody. METHODS: Forty-four children with SLE were enrolled in this study. As a control group, 30 children with other rheumatic diseases were also enrolled. Anti-mDNA and anti-dsDNA antibodies were measured by IIF. Anti-smooth muscle (Sm) antibodies were measured by immuno-double diffusion (ID) and IIF. RESULTS: Out of 44 juvenile SLE patients, 34 (77.27%) were seropositive for anti-mDNA, which was significantly higher than that of patients with other rheumatic diseases (20.00%, P<0.05). The sensitivity and specificity of anti-mDNA for juvenile SLE diagnosis were 77.27% and 80.00%, respectively. The positive predictive value and negative predictive value were 85.00% and 70.59%, respectively. The positive rate of anti-mDNA in SLE lacking of anti-dsDNA and anti-Sm antibodies were 68.00% (17/25) and 79.49% (31/39), respectively. CONCLUSION: The detection of anti-mDNA antibodies is useful for diagnosis of juvenile SLE, especially in patients who are negative for anti-dsDNA antibodies and anti-Sm antibodies.