Background:Baricitinib (BARI) is an oral selective inhibitor of Janus kinase 1 (JAK1) and JAK2. In the EU and some other countries, baricitinib has been approved for the treatment of moderately to severely active rheumatoid arthritis (RA) in adult patients. This abstract reports efficacy and safety results from a phase 3, double-blinded, 52-week study (RA-BALANCE) that enrolled patients (pts) in China, Argentina and Brazil (NCT02265705).Objectives:To assess the efficacy and safety of BARI vs placebo (PBO) in the treatment of RA.Methods:Patients with moderately to severely active RA (tender joint counts ≥6 & swollen joint counts ≥6 & hsCRP≥6 mg/L) despite stable background methotrexate (MTX), were randomized 1:1 to PBO (n=145) or BARI 4-mg (n=145) once daily (QD), stratified by country and baseline joint erosion status. Background MTX was continued. Non-responders were rescued from Week 16. At Week 24, pts receiving PBO were switched to BARI 4-mg QD. ACR20 at Week 12 was the primary endpoint and there were multiple secondary endpoints e.g., assessing physical function, low disease activity and pain.Results:The primary ACR20 response was significantly greater for BARI than PBO (58.6% vs 28.3%, p≤0.001, Table). At Weeks 12 and 24, significant improvements were seen in pts receiving BARI vs PBO for ACR20/50/70, DAS28-hsCRP, CDAI low disease activity and SDAI low disease activity, many as early as by Week 1. At Week 16, significantly less radiographic progression was seen in pts receiving BARI vs PBO and numerical improvement was observed at Week 24. At Week 12, significant improvement in HAQ-DI minimum clinically important difference ≥0.3 (physical function), duration of morning joint stiffness, severity of morning joint stiffness numeric rating scale (NRS), worst tiredness NRS and reduced pain (0–100 mm VAS) were seen in pts receiving BARI vs PBO.During Weeks 0–24, treatment emergent adverse events and infections were reported in 74.5% and 42.1% of BARI pts and 62.1% and 28.3% of PBO pts, respectively. Serious adverse events were reported in 2.8% of pts in both groups. There was 1 nonserious esophageal candidiasis in the BARI group for Week 0–24. Four herpes zoster events (1 PBO, 3 BARI) were reported for Week 0–24. No major cardiovascular events, deaths, tuberculosis, venous thromboembolic events or malignancies were reported in the study through Week 24 for PBO and through Week 52 for BARI group. No unexpected safety signals were observed.Table 1Study RA-BALANCE efficacy measuresConclusions:Compared to PBO, BARI provided significant improvements in control of signs and symptoms, including pain and physical function with an acceptable safety profile.Disclosure of Interest:Z. Li Consultant for: Advisory board member of baricitinib, J. Hu: None declared, C. Bao Consultant for: Advisory board member of baricitinib, X. Li Consultant for: Advisory board member of baricitinib, X. Li Consultant for: Advisory board member of baricitinib, J. Xu: None declared, A. Spindler: None declared, X. Zhang Consultant for: Advisory boa...
Evolving SACT modalities may facilitate an increased use of SACT at EOL and associated early mortality; however, in this cohort, decreased early mortality risk in the 2010-2014 timeframe suggests concomitant evolution of decisions regarding EOL SACT and/or palliative and EOL care may be underway at our centre, but represents an area for ongoing investigation.
Background: In the Phase III FLAURA trial (NCT02296125), osimertinib significantly improved PFS relative to SoC EGFR-TKIs (gefitinib/erlotinib) in patients with untreated Ex19del/L858R positive (EGFRm) NSCLC. EGFRm NSCLC tumors can exhibit high PD-L1 expression, an important biomarker for immunotherapy treatment decisions. The frequency and clinical relevance of exhibiting both biomarkers prior to treatment are unclear. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following EGFR-TKI treatment. Method: Tissue samples from 994 patients with advanced NSCLC were screened for EGFR Ex19del/L858R mutations for enrolment in FLAURA; 556 were randomized to treatment. 197 tissue-blocks from the screened population (including EGFR mutation-positive and -negative samples) were tested for PD-L1 using the SP263 (Ventana) immunohistochemical assay; positive tumour cell (TC) staining PD-L1 TC25% and TC1% thresholds were applied. PFS was investigatorassessed, per RECIST 1.1, according to PD-L1-expressers (TC1%) or -negatives (TC<1%) in randomized patients. Result: 193/197 blocks had sufficient tumor tissue for staining. 65/193 patients were EGFR mutation-negative. 128/193 patients were EGFR mutation-positive: 106/128 were randomized to treatment (osimertinib: 54; SoC: 52). The table presents PD-L1 expression according to EGFR mutation status. For PD-L1-expressers (TC1%), median PFS was 18.4 months for osimertinib and 6.9 months for SoC (HR 0.30 [95% CI 0.15, 0.60]). For PD-L1negative patients (TC<1%), median PFS was 18.9 months for osimertinib and 10.9 months for SoC (HR 0.37 [95% CI 0.17, 0.74]). Conclusion: There was PFS benefit with osimertinib versus SoC regardless of whether tumors were PD-L1-expressers (TC1%) or -negatives (TC<1%). Using the TC25% threshold, PD-L1 prevalence was lower in EGFR mutationpositive than mutation-negative samples; there were insufficient patients with TC25% tumors for PFS assessment. These results support the efficacy of EGFR-TKIs, including osimertinib, as first-line treatment of EGFRm advanced NSCLC, irrespective of PD-L1 expression.Background: In addition to the known resistant genetic alterations, such as de novo T790M and TP53 mutations, some recent studies suggested that other concomitant mutations might also compromise the efficacy of EGFR-TKIs. Meanwhile, it has been widely observed that EGFR 19 exon deletion (19del) was associated with better outcomes in treatments with EGFR-TKIs than L858R mutation (L858R). It is of interest to explore whether the respective mutational profiles of 19del and L858R may explain their different sensitivity to EGFR-TKIs. Method: We obtained individual patient data from 7 studies (including 1 from our center) using next generation sequencing to comprehensively determine the mutational profile of EGFR mutated patients. As different panels were used by different studies, we analyzed T790M, TP53 and the loci that were reported by at least 4 studies (half of the included ones). Result: A total of 250 19del ...
package R, to analyze the relationships between cognitive assessment results and clinical characteristics, and Kappa test was used to analyze the consistency of physical examination and cognitive scales for assessing the neurocognitive functions in patients. Finally, the related factors were analyzed with univariate and multivariate analysis. Results: Clinical physical examination showed that there were 21 cases of cognitive decline (28.4%) and 53 cases of normal cognition (71.6%), while the results of cognitive scales revealed that there were 6 cases of normal cognition (8.1%), 26 cases of mild impairment (35.1%), 2 cases of moderate impairment (2.7%) and 40 cases of severe impairment (54.1%). The result of Kappa test showed Kappa<0.4, indicating that the differences between cognitive scale results and physical examination were significant. The univariate analysis on the factors related to neurocognitive function impairment revealed that the risk factors that may affect the degree of neurocognitive function impairment included age, KPS score, GPA score, RPA class and the number of metastatic tumors; and the multivariate analysis showed that age and RPA class>2 were the independent risk factors for neurocognitive function impairment. Conclusion: Patients with brain metastasis from lung cancer have various degrees of neurocognitive function impairment before receiving radiotherapy. Compared with clinical physical examination, the cognitive scales can greatly improve the detection rate of neurocognitive function impairment. Age and RPA class>2 are considered as independent risk factors for neurocognitive function impairment.Background: Interstitial lung diseases (ILD) frequently occur in patients with lung cancer. The optimal treatment strategy for non-smallcell lung cancer (NSCLC) patients with ILD remains unclear. We reviewed the efficacy and safety of surgery, chemotherapy, and radiotherapy. Method: We analyzed the medical records of patients with clinical stage IIIA-N2 NSCLC with ILD who were treated at our hospital between 2001 and 2016. Results: 505 patients with clinical stage IIIA-N2 NSCLC were included. Of these patients with ILD, treatments included surgical resection (S) in 14 patients, chemoradiotherapy (CRT) in 7 patients, palliative chemotherapy (C) in 7 patients and palliative radiotherapy in one patient. The median follow-up period was 38 months. The patients' characteristics were as follows S/CRT/C: male, 26/6/7 patients; median age (range), 69 (58-82)/69 (60-75)/69 (35-82) years. Of the S, pathological stage IA/IIA/IIB/IIIA/IIIB, 1/1/2/ 9/1 patients. The median progression-free survival times were 9.5 months (95% CI: 5.3-45.3 months) in S, 45.9 months (95% CI: 7.2 months-not reached [NR]) in CRT, and 5.0 months (95% CI: 0.5-10.5 months) in C. The median overall survival time were 33.3 months (95% CI: 9.8 months-NR) in S, 45.9 months (95% CI: 8.3 months-NR) in CRT, and 9.9 months (95% CI: 1.6-42.4 months) in C. One patient died within 1 month of surgical resection. Acute exacerbations of ILD (AE-IL...
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