Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10 10 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10 10 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov , NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more t...
INTRODUCTION: Sorafenib (SOR) is a potent multikinase inhibitor with anti-angiogenic and anti-proliferation activity. It is indicated for the treatment of advanced renal cell carcinoma and unresectable hepatocellular carcinoma. As a single agent, SOR has shown modest activity in patients with advanced BC. Here, we report results from one (SOLTI-0701) of four Phase 2b trials of sorafenib in combination with chemotherapy for advanced breast cancer.METHODS: SOLTI-0701 is a multinational, double-blind, randomized, placebo-controlled phase 2b study in patients with locally advanced or metastatic BC. Eligibility criteria included HER-2 negative tumors and <2 prior chemo regimens for advanced/metastatic BC. Patients with active brain metastasis were excluded. Patients were randomized (1:1) to receive CAP (1000 mg/m2, orally, twice daily [BID], for 14 of every 21 days) with placebo (pl) or SOR (400 mg, orally, BID, continuously). Randomization is stratified by metastatic site (visceral vs nonvisceral). The primary endpoint is progression-free survival (PFS), and secondary endpoints include overall survival, time to progression, response rate, response duration, safety, and QoL. Disease assessments occur every 6 weeks for the first 24 weeks of the study and then every 9 weeks thereafter until disease progression. Based on projected event and accrual rates, a sample size of 220 patients has been calculated. We estimate 120 PFS events within 17 months of study initiation. The study is registered at EudraCT (ID 2007-000290-32).RESULTS: Enrollment began in August 2007 and was completed in December 2008 with 229 patients randomized. Study findings demonstrated that the median PFS was extended in patients treated with SOR and CAP compared to patients receiving CAP and PL. These results were statistically significant (p=0.0006). The safety and tolerability of the combination did not show any new or unexpected toxicities. A subset analysis will be presented.CONCLUSION: The SOLTI-0701 study will provide important efficacy and safety data for the use of sorafenib in combination with oral chemotherapy for advanced breast cancer. These data will help us better understand the potential role for sorafenib in BC and if phase III trials are warranted. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 45.
<b><i>Introduction:</i></b> Pancreatic surgery still carries a high morbidity and mortality even in specialized centers. The aim of this study was to evaluate the influence of patients’ body composition on postoperative complications and survival after pancreatic surgery. <b><i>Methods:</i></b> This was a retrospective study on patients undergoing pancreatic surgery between March 2012 and December 2017. Demographics, clinical data, and postoperative complications classified according to Clavien-Dindo were recorded. Body composition was assessed using routine diagnostic or staging computed tomography (CT). Multiple Cox proportional hazards models were adjusted. <b><i>Results:</i></b> Ninety patients were included, 55% were male, and the mean age was 68 ± 10.9 years. Of these 90, 92% had a total pancreatectomy or pancreaticoduodenectomy, 7% a distal pancreatectomy, and 1% a pancreaticoduodenectomy with multi-visceral resection; 84% had malignant disease. The incidence of major complications was 27.8% and the 90-day mortality was 8.8%. The ratio of visceral fat area/skeletal muscle area (VFA:SMA) was associated with an increased risk of complications (OR 2.24, 95% CI 1.14–4.87, <i>p</i> = 0.03) and 90-day survival (HR 2.13, 95% CI 1.13–4.01, <i>p</i> = 0.019). On simple analysis, shorter overall survival (OS) was observed in patients aged ≥70 years (<i>p</i> = 0.0009), with postoperative complications ≥IIIb (<i>p</i> = 0.01), an increased VFA:SMA (<i>p</i> = 0.007), and decreased muscle radiation attenuation (<i>p</i> = 1.6 × 10<sup>–5</sup>). In an OS model adjusted for age, disease malignancy, postoperative complications, and body composition parameters, muscle radiation attenuation remained significantly associated with survival (HR 0.94, 95% CI 0.90–0.98, <i>p</i> = 0.0016). A model which included only body composition variables had a discrimination ability (<i>C</i>-statistic 0.76) superior to a model which comprised conventional clinical variables (<i>C</i>-statistic 0.68). <b><i>Conclusion:</i></b> Body composition is a major determinant of postoperative complications and survival in pancreatic surgery patients.
At present, for patients with metastatic and castration-resistant prostate cancer, European Society for Medical Oncology and National Comprehensive Cancer Network guidelines recommend enzalutamide (E) or abiraterone (A). There are still a few studies comparing both drugs in a real-world setting, thus, in this article, we discuss an outcomes management methodology, supporting the follow-up of patients. This involves measuring relevant baseline traits and outcomes, such as overall survival (OS), treatment duration, patient-reported outcomes, and adverse events. We include 38 men in the A group and 15 in the E group. When comparing the survival of both drugs, both present similar OS. Regarding the quality-of-life analysis (QoL) with EPIC26, reported Standard QoL score was 58.3% in our patients, which was in line with the European Organization for the Research and Treatment of Cancer reference. As a result, by showing that we can capture the distinctive clinical benefits of A and E, and that patient-reported outcomes can be systematically collected for more than 2 years per living patient, we can now incorporate these findings in clinical discussions, risk-sharing agreements, or policy-level arguments.
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