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BACKGROUND Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that is selective for EGFR-TKI-sensitizing and EGFR T790M resistance mutations. Evidence suggests that the addition of chemotherapy may extend the benefits of EGFR-TKI therapy. METHODS In this phase 3, international, open-label trial, we randomly assigned in a 1:1 ratio patients with EGFR-mutated (exon 19 deletion or L858R mutation) advanced non-small-cell lung cancer (NSCLC) who had not previously received treatment for advanced disease to receive osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg per square meter of body-surface area] plus either cisplatin [75 mg per square meter] or carboplatin [pharmacologically guided dose]) or to receive osimertinib monotherapy (80 mg once daily). The primary end point was investigator-assessed progression-free survival. Response and safety were also assessed. RESULTS A total of 557 patients underwent randomization. Investigator-assessed progression-free survival was significantly longer in the osimertinib-chemotherapy group than in the osimertinib group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.49 to 0.79; PcO.OOl). At 24 months, 57% (95% CI, 50 to 63) of the patients in the osimertinib-chemotherapy group and 41% (95% CI, 35 to 47) of those in the osimertinib group were alive and progression-free. Progression-free survival as assessed according to blinded independent central review was consistent with the primary analysis (hazard ratio, 0.62; 95% CI, 0.48 to 0.80). An objective (complete or partial) response was observed in 83% of the patients in the osimertinib-chemotherapy group and in 76% of those in the osimertinib group; the median response duration was 24.0 months (95% CI, 20.9 to 27.8) and 15.3 months (95% CI, 12.7 to 19.4), respectively. The incidence of grade 3 or higher adverse events from any cause was higher with the combination than with monotherapy -- a finding driven by known chemotherapy-related adverse events. The safety profile of osimertinib plus pemetrexed and a platinum-based agent was consistent with the established profiles of the individual agents. CONCLUSIONS First-line treatment with osimertinib-chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR-mutated advanced NSCLC. [ABSTRACT FROM AUTHOR]

Quantitative changes in the concentration of rabbit serum proteins and glycoproteins accompanying a non-specific injury (terpentine oil inflammation) were studied by conventional electrophoretic and quantitative crossed immunoelectrophoretic analysis. Most significant changes were observed in the alpha2- and beta-globulin region as well as in some individual glycoproteins (haptoglobin, ceruloplasmin, IgM globulin). In the paper the parallel changes in sugar components of glycoproteins were also recorded.

The change in the protein concentration in blood serum was investigated after implantation of a pacing system with epoxide surface (group A, 20 patients) or metallic case (group B, 9 patients). The response to surgical intervention was equal in both groups. In the first period following operation the acute phase reaction took place in terms of increasing concentrations of alpha-globulins, especially alpha 1-acid glycoprotein, alpha 1-antitrypsin, ceruloplasmin, haptoglobin, and beta 1A/C-globulin, Simultaneously, a decrease in prealbumin, albumin, beta-globulin, in particular haemopexin and transferin concentration appeared. As for immunoglobulins, a decrease in IgG and increase in IgA and IgM globulins was observed. In the course of a longer period of time following implantation (group B--three months; group A--two years) a decrease of almost all investigated proteins was observed with exception of increased IgA globulin and transferin in group A.