Evolución del modelo de financiación de la investigación clínica en cáncer de mama durante las dos últimas décadas

En las últimas décadas el ámbito sanitario está presentando una rápida evolución, con un incremento de conocimientos aplicables a la investigación que conllevan notables mejorías de la práctica clínica. Pero, ¿quién tiene los conocimientos para realizar una investigación con adecuado rigor científico? ¿Qué nos capacita para investigar: contar con los medios o con los conocimientos necesarios? ¿Cuáles son los objetivos de la investigación, académicos o monetarios? Con este proyecto se pretende evaluar la evolución cronológica de los estudios aleatorizados con medicamentos y el cambio evolutivo en sus promotores durante las dos últimas décadas (1990-2010) en la investigación clínica del cáncer de mama a nivel internacional, considerando las fuentes de financiación de los estudios indexados en PUBMED en este periodo de tiempo, comparando a su vez estadio de la enfermedad en el que se desarrolla, grupo farmacológico evaluado en dichos proyectos de investigación, tamaño muestral o fase de desarrollo en la que se lleva a cabo según los autores. HIPÓTESIS Y OBJETIVOS: - HIPÓTESIS: El patrocinio y promoción de la investigación en cáncer de mama ha presentado un cambio durante las 2 últimas décadas, disminuyendo la participación de Grupos Cooperativos y financiación pública en el desarrollo de ensayos clínicos en el momento actual, incrementándose la financiación privada..

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC

Microangiopathic Hemolytic Anemia and Diffuse Bone Metastasis by Signet Ring Cell Adenocarcinoma

Tras largas discusiones, a lo largo del tiempo, entre contenidistas o referencialistas –que admiten la música de programa con una inspiración literaria o de otro ámbito–, frente a formalistas y absolutistas –para quienes la música carece de significado extramusical–, esta monografía trata las relaciones de música y palabra desde un punto de vista simbólico, que subyace de manera natural de las diversas manifestaciones artísticas como correspondencias entre texto y sonido. De esta manera, a través de la sinestesia, el encuentro de los sentidos, es posible trasladar el contenido simbólico de la poesía a la música, atendiendo a sus respectivos códigos de expresió

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

PURPOSE: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. PATIENTS AND METHODS: The study population includes 190 patients with stage I-III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of Cb (AUC 6) + D (75mg/m2) given every 21 days × 6 cycles. Pathological complete response (pCR: no evidence of invasive tumor in the breast and axilla) and Residual Cancer Burden (RCB) were evaluated. RESULTS: Among 190 patients, median tumor size was 35mm, 52% Lymph Node positive and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0+1 rates were 55% and 68%, respectively. pCR in patients with BRCA associated and wild-type TNBC were 59% and 56%, respectively (p=0.83). On multivariable analysis stage III disease was the only factor associated with a lower likelihood of achieving a pCR. 21% and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. CONCLUSION: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA associated and wildtype TNBC. These results are comparable to pCR achieved with addition of Cb to anthracycline-taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies

Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer.

Background: AKT pathway activation is implicated in endocrine-therapy resistance. Data on the efficacy and safety of the AKT inhibitor capivasertib, as an addition to fulvestrant therapy, in patients with hormone receptor-positive advanced breast cancer are limited. Methods: In a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had had a relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Patients were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors. Safety was assessed. Results: Overall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001). In the AKT pathway-altered population, the median progression-free survival was 7.3 months in the capivasertib-fulvestrant group, as compared with 3.1 months in the placebo-fulvestrant group (hazard ratio, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The most frequent adverse events of grade 3 or higher in patients receiving capivasertib-fulvestrant were rash (in 12.1% of patients, vs. in 0.3% of those receiving placebo-fulvestrant) and diarrhea (in 9.3% vs. 0.3%). Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo. Conclusions: Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. (Funded by AstraZeneca and the National Cancer Institute; CAPItello-291 ClinicalTrials.gov number, NCT04305496.)