of the original article, 'Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02'. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate, which is a chemotherapy with a linker (deruxtecan) joined to an antibody (trastuzumab). Trastuzumab binds to the human epidermal growth factor receptor 2 (HER2) protein on cancer cells, where it releases the chemotherapy to kill these cells. The DESTINY-PanTumor02 clinical study tested the effectiveness of T-DXd for people with various HER2-expressing cancers and the safety of treatment. Previous results from DESTINY-PanTumor02 showed that T-DXd had antitumor activity, and the greatest effects were seen in people with the highest tumor level of HER2 [defined as immunohistochemistry (IHC) 3+]. In this previous analysis, the HER2 expression was measured at a central laboratory. In clinical practice, HER2 expression will likely be measured at a local laboratory, so understanding whether T-DXd has similar effects regardless of how HER2 expression is measured is important. Here, we looked at the effects of T-DXd based on the HER2 test result used to determine a person's eligibility for the study, which could be measured using a local or central laboratory. In people with IHC 3+ tumors (where HER2 was measured at a local or central laboratory), 51% had a decrease in the size or number of tumors, according to established criteria (referred to as an objective response), while, in people with IHC 2+ tumors, 26% had an objective response. Side effects with T-DXd were consistent with previous studies. These results confirm T-DXd has antitumor effects in HER2-expressing cancers where the HER2 expression is measured by a local or central laboratory.
- Klíčová slova
- Advanced/metastatic solid tumors, HER2 testing, HER2-expressing, Trastuzumab deruxtecan,
- MeSH
- imunohistochemie MeSH
- imunokonjugáty * terapeutické užití škodlivé účinky MeSH
- kamptothecin * analogy a deriváty terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- klinické zkoušky, fáze II jako téma MeSH
- lidé MeSH
- nádory * farmakoterapie metabolismus patologie MeSH
- protinádorové látky imunologicky aktivní * terapeutické užití MeSH
- receptor erbB-2 * metabolismus MeSH
- sekundární analýza dat MeSH
- trastuzumab * terapeutické užití škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ERBB2 protein, human MeSH Prohlížeč
- imunokonjugáty * MeSH
- kamptothecin * MeSH
- protinádorové látky imunologicky aktivní * MeSH
- receptor erbB-2 * MeSH
- trastuzumab deruxtecan MeSH Prohlížeč
- trastuzumab * MeSH
IMPORTANCE: The Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study demonstrated that aspirin may be safely eliminated from the antithrombotic regimen after HeartMate 3 (HM3 [Abbott Cardiovascular]) left ventricular assist device (LVAD) implantation. This prespecified analysis explored whether conditions requiring aspirin (prior percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], stroke, or peripheral vascular disease [PVD]) would influence outcomes differentially with aspirin avoidance. OBJECTIVE: To analyze aspirin avoidance on hemocompatibility-related adverse events (HRAEs) at 1 year after implant in patients with a history of CABG, PCI, stroke, or PVD. DESIGN, SETTING, AND PARTICIPANTS: This was an international, multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial including patients implanted with a de novo HM3 LVAD across 51 centers. Data analysis was conducted from April to July 2024. INTERVENTIONS: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg per day) or placebo, in addition to a vitamin K antagonist (VKA) targeted to an international normalized ratio of 2 to 3 in both groups. MAIN OUTCOMES AND MEASURES: Primary end point (assessed for noninferiority) was a composite of survival free of any nonsurgical (>14 days after implant) HRAEs including stroke, pump thrombosis, bleeding, and arterial peripheral thromboembolism at 12 months. Secondary end points included nonsurgical bleeding, stroke, and pump thrombosis events. RESULTS: Among 589 of 628 patients (mean [SD] age, 57.1 [13.7] years; 456 male [77.4%]) who contributed to the primary end point analysis, a history of PCI, CABG, stroke, or PVD was present in 41% (240 of 589 patients). There was no interaction between the presence of an atherosclerotic vascular condition and effect of aspirin compared with placebo (P for interaction= .23). The preset 10% noninferiority margin was not crossed for the studied subgroup of patients. Thrombotic events were rare, with no differences between aspirin and placebo in patients with and without vascular disease (P for interaction = .77). Aspirin treatment was associated with a higher rate of nonsurgical major bleeding events in the group with prior vascular condition history compared with those without aspirin (rate ratio for placebo compared with aspirin, 0.52; 95% CI, 0.35-0.79). CONCLUSIONS AND RELEVANCE: Results of this prespecified analysis of the ARIES-HM3 randomized clinical trial demonstrate that in patients with advanced heart failure who have classical indications for antiplatelet therapy use at the time of LVAD implantation, aspirin avoidance was safe and not associated with increased thrombosis risk. Importantly, elimination of aspirin was associated with no increased thrombosis but a reduction in nonsurgical bleeding events in patients with a history of PCI, CABG, stroke, or PVD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.
- MeSH
- Aspirin * aplikace a dávkování MeSH
- ateroskleróza * komplikace MeSH
- cévní mozková příhoda MeSH
- dvojitá slepá metoda MeSH
- fibrinolytika terapeutické užití MeSH
- inhibitory agregace trombocytů * terapeutické užití MeSH
- koronární angioplastika MeSH
- krvácení chemicky indukované MeSH
- lidé středního věku MeSH
- lidé MeSH
- podpůrné srdeční systémy * škodlivé účinky MeSH
- prospektivní studie MeSH
- sekundární analýza dat MeSH
- senioři MeSH
- srdeční selhání * terapie chirurgie komplikace MeSH
- trombóza prevence a kontrola MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- komentáře MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- Aspirin * MeSH
- fibrinolytika MeSH
- inhibitory agregace trombocytů * MeSH
OBJECTIVES: Adherence to lifestyle interventions is crucial for the treatment of obesity. However, there is little research about adherence to lifestyle interventions in persons around retirement age. The objectives of this study are (1) to identify factors associated with the adherence to resistance training and a hypocaloric diet and (2) to describe the association between adherence and changes in body composition outcome parameters. DESIGN: This secondary data analysis included three randomized controlled trials. SETTING & PARTICIPANTS: The inclusion criteria of the participants were an age of 55-75 years, a BMI ≥ 25 kg/m2 and receiving both a hypocaloric diet and resistance training. All participants were residing in the community. MEASUREMENTS: Adherence to hypocaloric diet was measured through the mean dietary intake on the basis of a 3-day dietary record. If the participant consumed at least 600 kcal less than the individual caloric requirements, they were considered adherent. Adherence to resistance training was achieved if ≥67% of the recommended training sessions were attended over the course of the study periods. RESULTS: 232 participants were included, 47.0% female, mean age 64.0 (±5.5) years. 80.2% adhered to resistance training and 51.3% adhered to a hypocaloric diet. Older age (Beta 0.41; 95% CI 0.05, 0.78; p = 0.028) and male sex (Beta 7.7; 95% CI 3.6, 11; p < 0.001) were associated with higher resistance training adherence. A higher BMI at baseline (Beta 6.4; 95% CI 3.6, 9.2; p < 0.001) and male sex (Beta 65; 95% CI 41, 88; p < 0.001) were associated with higher adherence to hypocaloric diet. CONCLUSION: We identified several associated factors (sex, age and BMI at baseline) that should be considered to promote adherence in future lifestyle intervention studies in persons around retirement age. We recommend including behavior change techniques in lifestyle interventions and consider sex-specific interventions to improve the adherence of women.
- Klíčová slova
- Adherence, Hypocaloric diet, Obese, Overweight, Resistance training, Retirement age,
- MeSH
- adherence pacienta * statistika a číselné údaje MeSH
- důchod MeSH
- index tělesné hmotnosti MeSH
- kalorická restrikce * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- obezita dietoterapie MeSH
- odporový trénink * metody MeSH
- randomizované kontrolované studie jako téma MeSH
- redukční dieta metody MeSH
- sekundární analýza dat MeSH
- senioři MeSH
- složení těla MeSH
- životní styl MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH