Subcutaneous versus intravenous nivolumab for renal cell carcinoma.

BACKGROUND: The evolving oncology treatment paradigm has created an unmet need for administration options that improve patient experiences and health care efficiencies. PATIENTS AND METHODS: CheckMate 67T (NCT04810078) was a phase III, open-label, multicenter, noninferiority trial in which patients with advanced/metastatic clear cell renal cell carcinoma were randomized to subcutaneous nivolumab (1200 mg every 4 weeks; coformulated with recombinant human hyaluronidase PH20 20 000 units) or intravenous nivolumab (3 mg/kg every 2 weeks). The primary objective was to assess the noninferiority of subcutaneous versus intravenous nivolumab by coprimary endpoints determined from a population pharmacokinetics analysis [time-averaged serum concentration over the first 28 days (Cavgd28), and minimum steady-state serum concentration (Cminss); noninferiority threshold: lower boundary of 90% confidence interval (CI) of the geometric mean ratios (GMR) ≥0.8]. Objective response rate (ORR) was a key secondary endpoint powered for noninferiority [noninferiority threshold: lower boundary of 95% CI of relative risk of ORR (subcutaneous versus intravenous nivolumab) ≥0.60]. RESULTS: Overall, 495 patients were randomized. Relative exposure in the subcutaneous versus intravenous arm reported by the GMR of Cavgd28 and Cminss was 2.098 (90% CI 2.001-2.200) and 1.774 (90% CI 1.633-1.927), respectively. After 8 months of minimum follow-up, ORR was 24.2% with subcutaneous nivolumab (95% CI 19.0%-30.0%) versus 18.2% with intravenous nivolumab [95% CI 13.6%-23.6%; relative risk: 1.33 (95% CI 0.94-1.87)]. Coprimary endpoints and ORR met noninferiority thresholds. Additional efficacy and safety measures were similar. CONCLUSIONS: Subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and ORR. No new safety signals were observed.

Factors affecting SPF in vitro measurement and correlation with in vivo results.

OBJECTIVE: The in vitro evaluation of SPF is still a problem due to the lack of repeatability and correlation between the in vitro and in vivo data, and many authors are currently working to develop an internationally harmonized method. Very recently, the use of several "adjuvant" ingredients such as boosters, antioxidants, immunomodulators, solvents and film-forming ingredients have further complicated the pattern for product developers that should frequently run in vivo test. The aim of this study was to understand whether a simple and cheap in vitro method could be optimized in order to provide both statistically repeatable and predictive SPF measurement. METHODS: In vitro SPF assessments were carried out on 75 commercial products. The SPF was measured according to two laboratory methods (A and B), using different substrates (PMMA and surgical tape Transpore™), quantity of product and spectrophotometers. In order to evaluate whether a standard technique of spreading could lead to a statistically reliable result, we applied different spreading pressure (100 g and 200 g). Furthermore, we investigate whether other parameters characterizing the product (SPF category, filter and texture) might represent statically significant variables affecting the measures. We then compared the results obtained from in vitro SPF measure of 11 products to in vivo SPF, in order to assess the predictability of in vitro methods. RESULTS: Several problems were encountered in confirming the weakness of the in vitro procedures. Pressure, SPF category, filter and texture did not affect significantly the results. Overall best results were obtained with the B2 method that in terms of repeatability and predictivity provided statistically better results. Method A with Transpore™ tape showed better in vitro-in vivo correlation than Method B with PMMA plates. CONCLUSION: In our investigation, we demonstrated that it is possible for a single laboratory to optimize internal methods and protocols to achieve repeatable and predictive in vitro results, but it is extremely difficult to develop methods reproducible and equally reliable in different laboratories, probably due to "external variables" (e.g. environmental, operator), which are difficult to control.

Toxina botulínica: relación entre tipo de paciente y duración del efecto / Botulinum toxin: relation between patien type and duration of the effect

El uso de la Toxina Botulínica es frecuente en procedimientos de Cirugía Cosmética. Sin embargo, todavía quedan muchos aspectos que necesitan ser aclarados tales como los tipos de pacientes y la duración de su efecto. Si agrupamos los pacientes en diferentes modelos según su función muscular, podremos predecir la duración de ese efecto e informar adecuadamente a los pacientes. Estos modelos los denominamos cinético, hipercinético y hipertónico. El modelo cinético es el de aquellos pacientes que presentan una concordancia entre su expresividad facial y sus emociones y que muy probablemente solo necesitarán un tratamiento al año. El modelo hipercinético incluye a aquellos pacientes que no mueven sus músculos de acuerdo con su mímica; sus músculos faciales se contraen más rápidamente. En este caso la duración del tratamiento variará de los 4 a los6 meses. El modelo hipertónico lo encontramos en aquellos pacientes que son incapaces de relajar sus músculos faciales, en los que la duración del tratamiento solo será de 2 a 3meses. Esto es lo que puede hacer que en estos casos el tratamiento defraude tanto al paciente como al médico. Mediante esta comprensión del comportamiento muscular, cada paciente debe ser encajado en su grupo correspondiente de acuerdo a sus características musculares, lo que nos permitirá predecir la duración del efecto y guiar futuros tratamientos (AU)

The use of Botulinum Toxin is frequent in non surgical cosmetic procedures. Many aspects, though, still need clarification such as patient types and the duration of effect. By grouping the patients in different muscle pattern, the duration can be predicted and informed to patients. These groups consist of kinetic, hyperkinetic and hypertonic patterns. The kinetic pattern indicates that patients present a concordance with facial expression and emotions and they will probably need only one treatment per year. The hyperkinetic pattern refers to patients who do not move their muscles according to their mimicry. Facial muscles contract faster and the duration of the treatment will vary from 4 to 6months. The hypertonic pattern is found in those patients that are unable to relax their facial muscles and the duration maybe only from 2 to 3 months. That makes the treatment disappointing both for patients and injectors. By understanding the muscle behavior, the patient approach and their grouping according to specific muscle patterns, enables the prediction of duration and guidelines to future treatments (AU)

La anemia como factor pronóstico de recaída en cáncer de ovario / The anemia like factor prognosis of relapse in ovary cancer

Objetivos: evaluar nivel de hemoglonina previo a quimioterapia (Qt.) en cáncer de ovario como factor pronóstico de tiempo libre de progresión a la primera línea. Materiales y métodos: se analizaron retrospectivamente 58 pacientes (ptes) del Instituto Oncológico de Córdoba. Se definió anemia como hemoglobina menor a 12 g/dl. Se tomaron 2 grupos, el primero con anemia previa a la Qt. versus el segundo sin anemia. Se obtuvieron curvas de tiempo libre de progresión (TLP) y de supervivencia global (SG) con Kaplan Meier. El análisis de variables con Chi cuadrado y test t de Student. Resultados: anemia pre Qt.: 32 (55%). Sin anemia: 26 (45%). Todas tratadas con platino. TLP medio de 15; SG en anemia: 28,4; sin anemia: 59,8 meses. No se encontró asociación entre Hb y estadio, enfermedad residual, CA 125 inicial y patrón de recaída. Un alto porcentaje de ptes. sin anemia (88,5%) realizaron más de 4 ciclos de Qt. comparado con las anémicas (66%-p=0,04). Se observó mayor porcentaje de respuesta completa (RC) en ptes. sin anemia 54% vs 22%. Ptes. con anemia presentaron 60% de progresión de enfermedad vs. 30% en ptes. con nivel mayor de 12. Existe asociación significativa entre Hb y respuesta a Qt. (p = 0,01). Los que han manifestado beneficio clínico, tienen en mayor proporción de Hb mayor a 12. Las anémicas tienen 4 veces más posibilidades de presentar progresión. Conclusión: las ptes. sin anemia tuvieron un TLP y SG más prolongado y una mejor respuesta que las ptes. con anemia estadísticamente significativa. Palabras claves: cáncer de ovario - anemia - recaída - factor pronóstico - hemoglobina.