Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression.

BACKGROUND: In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%-100% predict for even greater benefit to pembrolizumab is currently unknown. PATIENTS AND METHODS: In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes . RESULTS: Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5-8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P < 0.001). Compared with patients with PD-L1 expression of 50%-89% (N = 107), patients with an expression level of 90%-100% (N = 80) had a significantly higher ORR (60.0% versus 32.7%, P < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33-0.74), P < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21-0.70), P = 0.002]. CONCLUSION: Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.

Combined use of risperidone and olanzapine in the treatment of patients with resistant schizophrenia: a preliminary case series report.

Polypharmacy, or the use of multiple drugs in the therapy of psychiatric disorders, is not recommended. However, appropriate combinations of pharmacologic mechanisms may enhance the efficacy of antipsychotic drugs and alter the course of schizophrenia. In recent years, some articles have been published about the successful use of clozapine and risperidone in combination for the treatment of patients with resistant schizophrenic and schizoaffective disorders. However, safety of this drug combination is open to discussion. This report presents the results of a preliminary study of five patients with resistant schizophrenia successfully treated with risperidone-olanzapine combination. The results suggest that this combination may be useful. In the future, the efficacy of risperidone-olanzapine combination should be confirmed in larger study populations before its clinical application is considered.

[The morphological characteristics of the cardiac lymphatic bed in chronic coronary failure]. / Morfologicheskie osobennosti limfaticheskogo rusla serdtsa pri khronicheskoi koronarnoi nedostatochnosti.

A study is presented of the morphological changes of the lymphatic circulation in chronic ischemic heart disease (IHD). Examinations were carried out on clinical material: intraoperative cardiac biopsies and on hearts of patients who died of this disease at the age of 36-59 years. Transmission electron microscopy was used. A clinical comparison was realized of changes of intramyocardial and subepicardial regions of the heart lymph circulation and morphological equivalents of disorders of outflow of lymph from the heart in chronic IHD were evaluated. The obtained data indicate the lymph stasis possessing cardiotoxic and sclerogenous properties is an essential pathogenetic factor of myocardial fibrotization in chronic coronary insufficiency.