PURPOSE Preclinical data suggest the combination of an anti–programmed death receptor 1 antibody plus dabrafenib and trametinib to have superior antitumor activity compared with dabrafenib plus trametinib alone. These observations are supported by translational evidence suggesting that immune checkpoint inhibitors plus targeted therapy may improve treatment outcomes in patients with BRAF V600–mutant metastatic melanoma. COMBI-i is a phase III trial evaluating spartalizumab, an anti–programmed death receptor 1 antibody, in combination with dabrafenib and trametinib (sparta-DabTram), versus placebo plus dabrafenib and trametinib (placebo-DabTram) in patients with BRAF V600–mutant unresectable or metastatic melanoma. METHODS Patients received spartalizumab 400 mg intravenously every 4 weeks plus dabrafenib 150 mg orally twice daily and trametinib 2 mg orally once daily or placebo-DabTram. Participants were age ≥ 18 years with unresectable or metastatic BRAF V600–mutant melanoma. The primary end point was investigator-assessed progression-free survival. Overall survival was a key secondary end point (ClinicalTrials.gov identifier: NCT02967692 ). RESULTS At data cutoff (July 1, 2020), the median progression-free survival was 16.2 months (95% CI, 12.7 to 23.9 months) in the sparta-DabTram arm versus 12.0 months (95% CI, 10.2 to 15.4 months) in the placebo-DabTram arm (hazard ratio, 0.82 [95% CI, 0.66 to 1.03]; P = .042 [one-sided; nonsignificant]). The objective response rates were 69% (183 of 267 patients) versus 64% (170 of 265 patients), respectively. Grade ≥ 3 treatment-related adverse events occurred in 55% (146 of 267) of patients in the sparta-DabTram arm and 33% (88 of 264) in the placebo-DabTram arm. CONCLUSION The study did not meet its primary end point; broad first-line use of sparta-DabTram is not supported by these results. Further biomarker-driven investigation may identify patient subpopulations who could benefit from checkpoint inhibitor plus targeted therapy combinations.

No abstract

9527 Background: Combination of immune checkpoint inhibitors and targeted therapy may produce durable and deep response in a higher proportion of pts with BRAF V600–mutant unresectable or metastatic melanoma. A recent report from the randomized, double-blind, placebo (PBO)-controlled Part 3 of the Phase 3 COMBI-i trial (NCT02967692) failed to show a statistically significant progression-free survival (PFS) benefit (hazard ratio (HR) of 0.82 (95% CI, 0.66‒1.03, p=.042)). Here, we report 3-year OS data from COMBI-i part 3. Methods: Eligible pts were randomized 1:1 to receive either S+D+T (n = 267; S 400 mg IV Q4W + D 150 mg orally BID + T 2 mg orally QD) or PBO+D+T (n = 265), until progression or unacceptable toxicity. Although the primary endpoint of PFS was not met, exploratory OS and safety analyses were performed. OS was summarized descriptively using Kaplan–Meier methods and HR was estimated using a stratified cox regression model. Results: As of October 19, 2021 (median follow-up, 42.8 months), the median OS was not reached in S+D+T arm and was 40.4 months with PBO+D+T (HR 0.796; 95% CI, 0.615‒1.029). There were 113 (42.3%) deaths in the S+D+T and 126 (47.5%) in the PBO+D+T. Estimated 2-year and 3-year OS rates were 67.7% (95% CI 61.6‒73.1) and 60.1% (95% CI 53.8‒65.8) with S+D+T vs 61.9% (95% CI 55.6‒67.5) and 52.9% (95% CI 46.6‒58.9) with PBO+D+T, respectively. An OS benefit was observed with S+D+T in these prespecified subgroups – Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1 (HR 0.50; 95% CI, 0.32‒0.8), age ≥65 years (HR 0.58; 95% CI, 0.36‒0.94), PD-L1 negative ( < 1%) (HR 0.62; 95% CI, 0.42‒0.91), sum of lesion diameters ≥ 66 mm at baseline (HR 0.63; 95% CI, 0.43‒0.91) and metastatic sites ≥ 3 (HR 0.66; 95% CI, 0.47‒0.94). Adverse events (AEs) irrespective of study treatment relationship were observed in 99.3% of pts in S+D+T vs 97.3% in PBO+D+T. The most common AEs (in > 30%; all grades) were pyrexia, diarrhea, and nausea. Grade ≥3 treatment-related AEs (TRAEs) occurred in 56.9% vs 35.2% of pts treated with S+D+T vs PBO+D+T, respectively. Dose reductions of D and T due to AEs were more frequent in the S+D+T arm than PBO+D+T arm (47.2% vs 25.4% and 45.7% vs 25.4%, respectively), contributing to a lower relative dose intensity; the TRAEs leading to discontinuation of all 3 study drugs occurred in 13.5% vs 8% of pts, respectively. Conclusions: Results from this landmark 3-year OS analysis from COMBI-i- part 3 was consistent with the primary analysis, while the PBO+D+T showed a higher OS rate than previously observed for D+T alone in COMBI D/V studies, with a longer median follow-up. Subgroup analyses showed that ECOG PS 1, age ≥65 years, negative PD-L1 status and high tumor burden were associated with better OS in S+D+T in terms of HR. Clinical trial information: NCT02967692.

Цель исследования: изучить выраженность стрессовой реакции организма во время операций на тол стой кишке путем определения концентрации «стрессовых гормонов» и уровня гликемии в условиях раз личных видов анестезий.Материалы и методы. Пациентов, перенесших резекционные операции на толстой кишке по поводу зло качественных заболеваний, разделили на 2 группы: основную (n=57) и группу сравнения (n=35). В основной группе проводили мультимодальную анестезию, включавшая неглубокую симпатическую блокаду в сочета нии с поверхностной ингаляционной анестезией. В группе сравнения была проведена ингаляционно внутри венная анестезия на основе системного введения фентанила в условиях миоплегии и инсуффляции севоф люрана. В трех исследовательских точках (перед индукцией в анестезию, в травматичный момент операции и в момент окончания операции) в сыворотке крови определяли содержание инсулина, адреналина, норадре налина, дофамина, кортизола и глюкозы. Проверка статистических гипотез проведена с помощью непараме трических методов, данные обработаны с использованием программы Statistica 6.Результаты. В группе сравнения во 2 й и 3 й точках отметили значительное увеличение содержания в сыворотке крови кортизола и катехоламинов. В основной группе эти показатели не превышали норматив ных значений. Содержание инсулина в основной группе было повышено в 1 й и 2 й точках, а в конце опе рации -понижено по отношению к группе сравнения. Гликемический профиль оказался практически иден тичным с тенденцией к гипергликемии в группе сравнения.Заключение. На основании полученных результатов можно утверждать, что мультимодальная анесте зия обладает большим стресс протективным действием во время травматичных операций. Соотношение значений инсулина и глюкозы в группах указывает на способность мультимодальной анестезии предупреж дать послеоперационную инсулинорезистентность.Ключевые слова: рак толстой кишки; мультимодальная анестезия; стресс; кортизол; инсулин; адреналин; норадреналин; дофамин; глюкоза Objective: to investigate the severity of the stress response of the organism during surgery on the colon because of a tumor by determining the level of stress hormones and glucose depending on various types of anesthesia. Materials and methods.Patients who have undergone resection surgery because of the colon malignancy were divided into two groups: the study group (n=57) and comparison group (n=35). In the study group a multimodal anesthesia was performed that included a shallow sympathetic blockade in combination with surface inhalation anesthesia. In the comparison group inhalation intravenous anesthesia was performed on the basis of systemic О Б Щ А Я Р Е А Н И М А Т О Л О Г И Я , 2 0 1 6 , 1 2 ; 2 57 Вопросы анестезиологии w w w . r e a n i m a t o l o g y . c o m

Treatment of benign prostatic hyperplasia is an important and challenging problem of modern medicine. One of the most modern methods of the treatment of this disease is prostatic artery embolization. This procedure is most often done through transfemoral approach. Transradial vascular access has many advantages over the transfemoral access. Our study presents a comparative analysis of the use of transradial and transfemoral approach in this type of interventions. Transradial access was used in 13 patients, and transfemoral access - in 12 patients. The success of the procedure was 100% in both groups. The total duration of the procedure, the time needed for catheterization of internal iliac and prostatic arteries and the radiation exposure were significantly lower in the transradial approach group. There were no significant differences in the incidence of complications between two groups. The use of the transradial access was associated with a significant reduction of the frequency and severity of the discomfort associated with the procedure. Transradial approach has numerous advantages over the transfemoral approach and may have great clinical significance.