Summary Background The risk of venous thromboembolism is high after total hip arthroplasty and could persist after hospital discharge. Our aim was to compare the use of rivaroxaban for extended ...thromboprophylaxis with short-term thromboprophylaxis with enoxaparin. Methods 2509 patients scheduled to undergo elective total hip arthroplasty were randomly assigned, stratified according to centre, with a computer-generated randomisation code, to receive oral rivaroxaban 10 mg once daily for 31–39 days (with placebo injection for 10–14 days; n=1252), or enoxaparin 40 mg once daily subcutaneously for 10–14 days (with placebo tablet for 31–39 days; n=1257). The primary efficacy outcome was the composite of deep-vein thrombosis (symptomatic or asymptomatic detected by mandatory, bilateral venography), non-fatal pulmonary embolism, and all-cause mortality up to day 30–42. Analyses were done in the modified intention-to-treat population, which consisted of all patients who had received at least one dose of study medication, had undergone planned surgery, and had adequate assessment of thromboembolism. This study is registered at ClinicalTrials.gov , number NCT00332020. Findings The modified intention-to-treat population for the analysis of the primary efficacy outcome consisted of 864 patients in the rivaroxaban group and 869 in the enoxaparin group. The primary outcome occurred in 17 (2·0%) patients in the rivaroxaban group, compared with 81 (9·3%) in the enoxaparin group (absolute risk reduction 7·3%, 95% CI 5·2–9·4; p<0·0001). The incidence of any on-treatment bleeding was much the same in both groups (81 6·6% events in 1228 patients in the rivaroxaban safety population vs 68 5·5% of 1229 patients in the enoxaparin safety population; p=0·25). Interpretation Extended thromboprophylaxis with rivaroxaban was significantly more effective than short-term enoxaparin plus placebo for the prevention of venous thromboembolism, including symptomatic events, in patients undergoing total hip arthroplasty. Funding Bayer HealthCare AG, Johnson & Johnson Pharmaceutical Research and Development LLC.
Summary Background Addition of bevacizumab to standard chemotherapy in the neoadjuvant setting in patients with HER2-negative metastatic breast cancer improves progression-free survival and the ...proportion of patients achieving pathological complete response. In the BEVERLY-1 (UCBG-0802) trial we aimed to assess the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy in the treatment of patients with HER2-negative inflammatory breast cancer. Methods We did this phase 2, single-arm trial at 20 hospitals in France. We enrolled women aged 18 years or older who had non-metastatic HER2-negative inflammatory breast cancer. Patients underwent 3-week treatment cycles, receiving neoadjuvant intravenous fluorouracil (500 mg/m2 ), epirubicin (100 mg/m2 ), cyclophosphamide (500 mg/m2 ), and bevacizumab (15 mg/kg) during cycles 1–4, then docetaxel (100 mg/m2 ) and bevacizumab during cycles 5–8. 2–4 weeks after surgery, patients received adjuvant radiotherapy, hormone therapy (if they had a hormone receptor-positive tumour), and adjuvant intravenous bevacizumab. The primary endpoint was pathological complete response in breast and axillary lymph nodes after neoadjuvant treatment, determined after centralised review in accordance with Sataloff classification and assessed in the intention-to-treat population. Our analysis of toxic effects included all patients who received at least one dose of bevacizumab. The trial is complete and follow-up is ongoing. This study is registered with ClinicalTrials.gov , number NCT00820547. Findings Between Jan 16, 2009, and Sept 8, 2010, we enrolled 101 patients, one of whom withdrew consent before treatment, leaving 100 patients in the primary endpoint analysis. After neoadjuvant therapy, 19 (19% 95% CI 12–28; p=0·16) of 100 patients achieved a pathological complete response according to centralised review. The most frequent grade 3–4 events during the neoadjuvant phase were neutropenia (89 89% of 100 patients), febrile neutropenia (37 37%), and mucositis (23 23%) and during the adjuvant phase the most frequent grade 3–4 adverse event was proteinuria (5 7% of 75 patients). One (1%) patient died of thrombotic microangiopathy after cycle 1, which was thought to be related to bevacizumab. Two patients (3%) developed transitory heart failure. 48 (48%) patients had serious adverse events, the most frequent of which was febrile neutropenia (28 28%). Interpretation Our results suggest that the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy does not provide clinical benefit to patients with non-metastatic HER2-negative inflammatory breast cancer. Longer follow-up and correlative studies to identify patients who might benefit from bevacizumab are needed. Funding Roche, La Ligue Nationale contre le Cancer, UNICANCER, and Chugai Pharma.
