Sequencing of Cabazitaxel and Abiraterone Acetate After Docetaxel in Metastatic Castration-Resistant Prostate Cancer: Treatment Patterns and Clinical Outcomes in Multicenter Community-Based US Oncology Practices

AbstractBackgroundOptimal sequencing of cabazitaxel (C) and abiraterone acetate (A) after docetaxel (D) for metastatic castration-resistant prostate cancer (mCRPC) is unclear. We assessed treatment patterns and outcomes in patients with mCRPC receiving different sequences of A or C, or both, after administration of D.MethodsRetrospective analysis was conducted of US Oncology Network iKnowMed (iKM) electronic health record (EHR) data to assess patients with mCRPC who received treatment with D and were subsequently treated with C or A, or both, between April 2011 and May 2012. Patients received 2 or 3 drugs: DA, DC, DAC, or DCA. Overall survival (OS) and time to treatment failure (TTF) were analyzed by the Kaplan-Meier method from the start to the end of second-line therapy after administration of D (TTF1) and to the end of combined second- and third-line therapy (TTF2) for 3-drug sequences. Multivariable Cox proportional hazard models evaluated the impact of baseline clinical prognostic factors and treatment sequence on OS and TTF.ResultsOf 350 patients who were treated with D and subsequent therapies, 183 (52.3%) received DA, 54 (15.4%) received DC, 77 (22.0%) received DCA, and 36 (10.3%) received DAC. In a multivariable analysis, adjusted comparisons suggested that 3-drug sequences were associated with improved OS versus 2-drug sequences (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.092-0.476; P = .0002). There were no statistically significant differences in OS and TTF for DC versus DA, and OS was significantly greater for DCA versus DAC (HR, 0.13; 95% CI, 0.022-0.733; P = .0210). More cycles of C were administered in DCA than in DAC (median 6 vs. 4; t test P < .0001), whereas the duration of A treatment was similar.ConclusionAdministration of 3 agents in the DCA sequence was more optimal for treating mCRPC in this hypothesis-generating study

Awareness of stroke among patients with chronic kidney disease on hemodialysis: a cross-sectional study

ABSTRACT BACKGROUND: Stroke is a major cause of mortality worldwide. Renal dysfunction is an important risk factor for stroke. Brazilian studies on stroke knowledge are generally population based. Studies stratifying stroke knowledge according to comorbidities are rare. Scientific data are essential to guide the awareness of stroke. OBJECTIVE: To assess stroke knowledge in patients with chronic kidney disease (CKD) on hemodialysis. DESIGN AND SETTING: Cross-sectional analytical study of patients with CKD on hemodialysis in north-eastern Brazil. METHODS: A self-administered questionnaire survey on stroke awareness was administered to patients with CKD on hemodialysis between April and November 2022. The chi-square test and other descriptive statistics were used. Univariate and multivariate analyses were performed using logistic regression. RESULTS: A total of 197 patients were included in the analysis. The Brazilian acronym for stroke was used by 53.5% of the participants. Less than 10.0% of the sample showed optimal decision-making ability regarding stroke. Of the participants, 29.9% knew at least one risk factor and one symptom; however, this was considered as having below the minimum capacity because they did not know the emergency service call number. In the analysis adjusted for income and education, females (odds ratio [OR], 0.40%; 95% confidence interval [CI], 0.20-0.82), older patients (OR, 0.24%; 95% CI, 0.09-0.63) and having at most one comorbidity (OR, 0.48%; 95% CI, 0.23-0.98) were factors for lower levels of knowledge or ideal decision-making capacity against stroke. CONCLUSIONS: Patients on hemodialysis, especially women and older people, have little knowledge about stroke

Tisotumab Vedotin in Combination with Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer:Results from the innovaTV 205/GOG-3024/ENGOT-cx8 Study

PURPOSE Tissue factor is highly expressed in cervical carcinoma and can be targeted by tisotumab vedotin (TV), an antibody-drug conjugate. This phase Ib/II study evaluated TV in combination with bevacizumab, pembrolizumab, or carboplatin for recurrent or metastatic cervical cancer (r/mCC). METHODS This open-label, multicenter study (ClinicalTrials.gov identifier: NCT03786081) included dose-escalation arms that assessed dose-limiting toxicities (DLTs) and identified the recommended phase II dose (RP2D) of TV in combination with bevacizumab (arm A), pembrolizumab (arm B), or carboplatin (arm C). The dose-expansion arms evaluated TV antitumor activity and safety at RP2D in combination with carboplatin as first-line (1L) treatment (arm D) or with pembrolizumab as 1L (arm E) or second-/third-line (2L/3L) treatment (arm F). The primary end point of dose expansion was objective response rate (ORR). RESULTS A total of 142 patients were enrolled. In dose escalation (n = 41), no DLTs were observed; the RP2D was TV 2 mg/kg plus bevacizumab 15 mg/kg on day 1 once every 3 weeks, pembrolizumab 200 mg on day 1 once every 3 weeks, or carboplatin AUC 5 on day 1 once every 3 weeks. In dose expansion (n = 101), the ORR was 54.5% (n/N, 18/33; 95% CI, 36.4 to 71.9) with 1L TV + carboplatin (arm D), 40.6% (n/N, 13/32; 95% CI, 23.7 to 59.4) with 1L TV + pembrolizumab (arm E), and 35.3% (12/34; 19.7 to 53.5) with 2L/3L TV + pembrolizumab (arm F). The median duration of response was 8.6 months, not reached, and 14.1 months, in arms D, E, and F, respectively. Grade ≥3 adverse events (≥15%) were anemia, diarrhea, nausea, and thrombocytopenia in arm D and anemia in arm F (none ≥15%, arm E).CONCLUSION TV in combination with bevacizumab, carboplatin, or pembrolizumab demonstrated manageable safety and encouraging antitumor activity in treatment-naive and previously treated r/mCC.</p

Exposure‐safety and exposure‐efficacy analyses for tisotumab vedotin for patients with locally advanced or metastatic solid tumors

Abstract The antibody‐drug conjugate (ADC) tisotumab vedotin (TV) received accelerated approval from the US Food and Drug Administration for treatment of adults with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. A population pharmacokinetic (PK) model, developed using dosing data from four clinical TV studies, was used to estimate individual exposure and explore safety and efficacy exposure‐response (ER) relationships. Because PK analysis showed no appreciable accumulation of TV and monomethyl auristatin E (MMAE) with repeated dosing, cycle 1 exposure metrics and predicted average concentrations from time zero until end of the cycle in which an event occurred (CavgLast) were used for ER analyses. The probability of achieving objective response increased significantly as the ADC cycle 1 maximum serum concentration (Cmax) increased. The probability of treatment‐related adverse events (AEs) leading to dose modification increased significantly as ADC cycle 1 area under the concentration‐time curve (AUC) increased. Number of grade 2+ ocular AEs increased significantly as ADC cycle 1 AUC, Cmax, and ADC CavgLast increased. MMAE cycle 1 AUC predicted risk of serious treatment‐related AEs. The relationship between ADC exposure and efficacy end points suggests ADC treatment was associated with clinically meaningful response across the observed exposures; greater exposure was associated with increased efficacy. The relationship between ADC and MMAE exposure and safety end points suggests increased exposure was associated with increased AE risk. These results align with clinical findings showing TV 2 mg/kg (≤200 mg for patients ≥100 kg) every 3 weeks is efficacious and tolerable for patients with r/mCC

Desenvolvimento de um modelo reduzido didático qualitativo e quantitativo de viga hiperestática

O uso de modelos reduzidos didáticos qualitativos e quantitativos pode auxiliar no ensino de cursos de Engenharia. Tendo isso em vista, se desenvolveu um modelo de viga hiperestática de um vão, engastada-apoiada, que permite comparar os deslocamentos e a reação do apoio rotulado, obtidos teoricamente em sala de aula com os valores medidos no modelo, o que é de grande ajuda no ensino das disciplinas de Resistência dos Materiais e Análise de Estruturas. Na extremidade rotulada, consta uma mini-balança que permite registrar a reação de apoio para cada situação de carregamento. As agulhas fixadas ao longo da viga permitem medir os deslocamentos verticais em várias posições da viga, por meio de um papel milimetrado fixado próximo a viga. Obteve-se uma boa relação entre os deslocamentos e as reações calculados com os medidos no modelo, demonstrando sua eficiência para ilustrar os métodos e conceitos no ensino da engenharia