Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer with PD-L1 ≥ 1 %: A subgroup analysis from the EMPOWER-Lung 3 part 2 trial.

Objectives: EMPOWER-Lung 3 part 2 (NCT03409614), a double-blind, placebo-controlled phase 3 study, assessed cemiplimab (anti-programmed cell death protein 1) plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer (NSCLC) without EGFR, ALK, or ROS1 aberrations, regardless of histology or PD-L1 expression levels. We report results from subgroup analysis of patients with PD-L1 expression ≥ 1 %.

Materials And Methods: Patients were randomized to receive cemiplimab 350 mg or placebo with chemotherapy every 3 weeks for up to 108 weeks.

Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3.

Background: EMPOWER-Lung 3, a randomized 2:1 phase 3 trial, showed clinically meaningful and statistically significant overall survival improvement with cemiplimab plus platinum-doublet chemotherapy versus placebo plus chemotherapy for first-line treatment of advanced non-small cell lung cancer. This study evaluated patient-reported outcomes (PROs).

Methods: PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks) for the first six doses, and then at start of every three cycles, using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) and Quality of Life-Lung Cancer Module (QLQ-LC13) questionnaires.

Cemiplimab Plus Chemotherapy Versus Chemotherapy Alone in Advanced NSCLC: 2-Year Follow-Up From the Phase 3 EMPOWER-Lung 3 Part 2 Trial.

Introduction: EMPOWER-Lung 3 part 2 (NCT03409614), a double-blind, placebo-controlled phase 3 study, investigated cemiplimab (antiprogrammed cell death protein 1) plus chemotherapy versus placebo plus chemotherapy in patients with advanced NSCLC without EGFR, ALK, or ROS1 aberrations, with either squamous or nonsquamous histology, irrespective of programmed death-ligand 1 levels. At primary analysis, after 16.4 months of follow-up, cemiplimab plus chemotherapy improved median overall survival (OS) versus chemotherapy alone (21.

Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial.

First-line cemiplimab (anti-programmed cell death-1 (PD-1)) monotherapy has previously shown significant improvement in overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced non-small cell lung cancer (aNSCLC) and PD-ligand 1 (PD-L1) expression ≥50%. EMPOWER-Lung 3 ( NCT03409614 ), a double-blind, placebo-controlled, phase 3 study, examined cemiplimab plus platinum-doublet chemotherapy as first-line treatment for aNSCLC, irrespective of PD-L1 expression or histology. In this study, 466 patients with stage III/IV aNSCLC without EGFR, ALK or ROS1 genomic tumor aberrations were randomized (2:1) to receive cemiplimab 350 mg (n = 312) or placebo (n = 154) every 3 weeks for up to 108 weeks in combination with four cycles of platinum-doublet chemotherapy (followed by pemetrexed maintenance as indicated).

Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial.

Background: Few prospective studies have compared poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors to chemotherapy for the treatment of BRCA1-mutated or BRCA2-mutated ovarian carcinoma. We aimed to assess rucaparib versus platinum-based and non-platinum-based chemotherapy in this setting.

Methods: In this open-label, randomised, controlled, phase 3 study (ARIEL4), conducted in 64 hospitals and cancer centres across 12 countries (Brazil, Canada, Czech Republic, Hungary, Israel, Italy, Poland, Russia, Spain, Ukraine, the UK, and the USA), we recruited patients aged 18 years and older with BRCA1-mutated or BRCA2-mutated ovarian carcinoma, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and who had received two or more previous chemotherapy regimens.

Novel PD-1 inhibitor prolgolimab: expanding non-resectable/metastatic melanoma therapy choice.

Background: Prolgolimab is an IgG1 anti-PD-1 (programmed cell death protein 1) monoclonal antibody containing the Fc-silencing 'LALA' mutation. We assessed the efficacy and safety of two dosing regimens of prolgolimab in patients with advanced melanoma in a multicenter open-label parallel-arm phase II trial (MIRACULUM). We present the final analysis after 1 year of follow-up and additional efficacy results from 2 years of follow-up.

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial.

Background: We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%.

Methods: In EMPOWER-Lung 1, a multicentre, open-label, global, phase 3 study, eligible patients recruited in 138 clinics from 24 countries (aged ≥18 years with histologically or cytologically confirmed advanced non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0-1; never-smokers were ineligible) were randomly assigned (1:1) to cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression.

Atezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study.

Background: Understanding the impact of the tumor immune microenvironment and BRCA1/2-related DNA repair deficiencies on the clinical activity of immune checkpoint inhibitors may help optimize both patient and treatment selection in metastatic triple-negative breast cancer. In this substudy from the phase 3 IMpassion130 trial, immune biomarkers and BRCA1/2 alterations were evaluated for association with clinical benefit with atezolizumab and nab-paclitaxel (A+nP) vs placebo and nP in unresectable (P+nP) locally advanced or metastatic triple-negative breast cancer.

Methods: Patients were randomly assigned 1:1 to nab-paclitaxel 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) and atezolizumab 840 mg every 2 weeks or placebo until progression or toxicity.

Chicken embryos can maintain heart rate during hypoxia on day 4 of incubation.

Acute exposure to hypoxic conditions is a frequent natural event during the development of bird eggs. However, little is known about the effect of such exposure on the ability of young embryos in which cardiovascular regulation is not yet developed to maintain a normal heart rate (HR). To address this question, we studied the effect of 10-20 min of exposure to moderate or severe acute hypoxia (10% or 5% O, respectively) on the HR of day 4 (D4) chicken embryos.

Correction: A phase 2 randomised study of veliparib plus FOLFIRI±bevacizumab versus placebo plus FOLFIRI±bevacizumab in metastatic colorectal cancer.

The original version of this article contained an error in Figure 1a. The number of patients at risk listed in the Veliparib arm of Figure 1a should have read "65" instead of "35".An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A phase 2 randomised study of veliparib plus FOLFIRI±bevacizumab versus placebo plus FOLFIRI±bevacizumab in metastatic colorectal cancer.

Background: Metastatic colorectal cancer (mCRC) has low survival rates. We assessed if addition of veliparib, concurrent to FOLFIRI, improves survival in patients with previously untreated mCRC.

Methods: This study compared veliparib (200 mg BID for 7 days of each 14-day cycle) to placebo, each with FOLFIRI.

[INFLUENCE OF AGGRESSION AND RELATED PSYCHOLOGICAL CHARACTERISTICS OF ATHLETES IN THE FREQUENCY OF NUCLEAR VIOLATIONS IN EXFOLIATED CELLS OF THE ORAL CAVITY].

The frequency of cells with abnormal nuclear morphology (micronuclei, perinuclear vacuo-les, notches, protrusions, such as «tongue» and «broken egg») in the buccal epithelium of wrestlers on different days of the competition period was identified. The largest number of violations observed on the 3rd day after the competition. It was conducted psychological testing of athletes and it was determined 16 psychological characteristics associated with the aggressiveness of athletes.

[THE INFLUENCE OF SEROTONIN TRANSPORTER AND MONOAMINE OXIDASE A GENES POLYMORPHISM ON PSYCHO-EMOTION AND KARYOLOGICAL STABILITY OF ATHLETES].

The influence of polymorphism of the serotonin transporter and monoamine oxidase A genes, associated with man's aggressiveness on the psycho-emotional state and karyological status of single combat athletes. It was revealed that the carriers of less active ("short"), monoamine oxidase A gene variant have a high motivation to succeed and less rigidity and frustrated, compared to the carriers of more active ("long") version of the gene. Heterozygote carriers of less active ("short") variant of the serotonin transporter gene 5-HTTL had more physical aggression, guilt and were less frustrated compared with carriers of two long alleles.

[The study of the frequency of buccal epithelium cells with nuclear in athletes in dependence on the place got in the competition].

Cytogenetic homeostasis ofathletes involved in hand-to-hand armyfighting, depending on the outcome of the fight and the level of aggressiveness has been studied. Status of the genetic apparatus in athletes was evaluated in buccal epithelium with the use of micronucleus test, which is widely usedfor the determination of the influence of various factors on the genetic stability of the organism. Psychological testing of athletes was executed with the use of Spielberger’s State-Trait Anger Expression Inventory scale, Bass-Darky questionnaire for the diagnostics of aggression and hostile reactions, Eysenck Personality Questionnaire test for the evaluation ofpsychic conditions and method of U.

[Evaluation of antimutagenic properties of powdered malt and polymalt extracts with the use of micronucleus test].

There were performed studies of the occurrence of cells with pathologies in the buccal epithelium of volunteers who consume drinks based on mixtures ofpowdered malt and polymalt extracts of buckwheat, peas, corn and barley. There was shown their impact on the stability of the genetic material of examined cases. There was established activation of apoptosis, which leads to the elimination of cells with cytogenetic deteriorations.

[Micronucleus test of human oral buccal epithelium: problems, progress and prospects].

The articles by russian and foreign authors for the period from 2000 to 2012, devoted to the problems of application, analysis and interpretation of the results of micronucleus test in human buccal epithelium has been analyzed in the review. Nuclear abnormality founding in the cells of the oral mucosa has been described. The paper summarizes works devoted to the analysis of the influence of the micronucleus test methods (painting, taking scrapings) to its results.

[Effect of acute hypoxia on the mechanical and electrical properties of the isolated skeletal muscles in the last third of chick embryogenesis].

The age-related changes of the contractile and electrical responses of the fast (m. tibialis anterior) and slow (m. soleus) isolated skeletal muscles and their changes under acute hypoxia were estimated during the 16-20 days of the chick embryogenesis.

[The effect of nuclear dyes on the frequency of aberrations in mucosal cells of humans].

The effect of staining with commonly used nuclear dyes (orsein, light green, methylene blue, azure-eosin by Romanovsky-Giemsa) on the frequency of occurrence of nuclear disorders (micronuclei, perinuclear vacuoles, notches, protrusions, such as "tongue" and "broken egg") in human buccal mucosa was determined. It is shown that Romanovsky-Giemsa dye is the best type of dye both in the quality of the micropreparations and the spectrum of detected abnormalities.

Physiological responses to acute changes in temperature and oxygenation in bird and reptile embryos.

Environmental conditions considerably influence embryogenesis and subsequent postnatal development; however, the roles of individual embryonic physiological systems in these effects remain largely unclear. Data on the effects of some environmental factors (temperature variation and hypoxia) on the development of embryos and extra-embryonic organs in reptiles and birds are summarized, with special emphasis on acute changes in these factors. The involvement of several physiological characteristics related to the functions of the extra-embryonic membranes, cardiovascular system, and embryonic behavior (amnion rhythmic contractions, cardiac activity, and embryonic motility) in the integrated response to temperature fluctuations and acute hypoxia is considered.

[Rhythmical contractile activity of amnion in embryogenesis of reptiles and birds].

Rhythmical contractile activity of amnion accompanies development reptiles and birds in the course of the large part of embryogenesis. These rhythmical contractions are myogenic and spontaneous. The strength, frequency, and character of the amnion contractions change in embryogenesis in a regular way.

[Effect of hypoxia on amnion rhythmic contractions and heart rate in the embryonic European pond turtle Emys orbicularis (Reptilia: Emydidae)].

The effect of acute hypoxia (10% O2 for 30 min) on the rate of amnion rhythmic contractions and heart rate (HR) was studied in two age groups of European pond turtle (Emys orbicularis) embryos, on days 19-27 and 37-43 of incubation (30-40 and 60-70% of the period until hatching). Under the control conditions, the two age groups of embryos did not differ from each other in either parameter. Hypoxia did not affect significantly the amnion contraction rate but decreased the HR.

Oxygen consumption as related to the development of the extraembryonic membranes and cardiovascular system in the European pond turtle (Emys orbicularis) embryogenesis.

The rate of oxygen consumption (V(O2)), embryo mass, distribution and mass of the chorioallantoic membrane (CAM), heart rate (HR), heart mass, and amnion rhythmic contractions (ARC) were studied in eggs of the European pond turtle (Emys orbicularis) incubated at 28 degrees C for 62.5+/-0.3 days.

[Treatment of neonatal respiratory distress syndrome with surfactant BL].

The paper presents the results of use of the Russian drug Surfactant BL as part of complex intensive care of respiratory distress syndrome (RDS) in the premature newborn. The drug was used in 45 children (a study group). A control group comprised 52 children with RDS who had undergone a course of therapy before the use of the drug at our clinic.