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The aim of this post hoc analysis of the VELOUR study (ClinicalTrials.gov NCT00561470) was to investigate the treatment effect of adding aflibercept to second-line infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) in patients with metastatic colorectal cancer (mCRC) who had failed any prior oxaliplatin-containing regimen. Adjuvant rapid relapsers (ARR), who were enrolled directly following relapse during or within 6 months of completion of oxaliplatin-containing adjuvant chemotherapy ( N  = 124, including 17 patients who also received bevacizumab as part of their adjuvant therapy), were excluded from the original VELOUR intention-to-treat (ITT) population ( N  = 1226). After exclusion of the ARR, overall survival (OS) in the ITT minus ARR (ITT-ARR) population ( N  = 1102) was longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm [hazard ratio (HR) 0.78, 95 % confidence interval (CI) 0.68–0.90; median survival difference 1.87 months]. In the subgroup of patients assigned to the prior bevacizumab stratum at randomization, OS was numerically longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm (HR 0.81; 95 % CI 0.63–1.04; median survival difference 2.14 months). Comparison of the post hoc analysis results with the primary analysis from VELOUR suggests that the inclusion of the directly enrolled ARR may have understated the aflibercept treatment benefit for both bevacizumab-pretreated and bevacizumab-naïve patients in the strictly second-line setting although no definitive conclusion may be inferred. The benefit associated with the addition of aflibercept to second-line FOLFIRI in patients with mCRC was observed whatever the timing of first-line disease progression. There were no unexpected safety concerns.

Treatment for relapsed/refractory multiple myeloma (RRMM) remains an unmet need. Isatuximab, an anti-CD38 monoclonal antibody has shown efficacy and tolerability as a monotherapy and combination therapy in Phase I/II studies in RRMM. Here, we describe the design of the Phase III ICARIA-MM study (NCT02990338) which will evaluate isatuximab in combination with pomalidomide (Pom) and low-dose dexamethasone (dex) (Pom/dex) versus Pom/dex alone in RRMM. Patients will be randomized in a 1:1 ratio. The primary endpoint is progression-free survival. Response will be determined by an independent response review committee using IMWG criteria (2016) and safety will be assessed throughout. Approximately 300 patients (150 in each arm) are expected to enroll. The first patient was recruited in January 2017 and accrual is ongoing.

Ombrabulin (AVE8062) disrupts the vasculature of established tumours and has shown preclinical synergistic anti-tumour activity when combined with cisplatin. In this phase 3 trial, we aimed to assess the efficacy and safety of ombrabulin plus cisplatin compared with placebo plus cisplatin in patients with advanced soft-tissue sarcomas. We did this multinational, randomised, double-blind, placebo-controlled phase 3 study at 44 centres in ten countries. Patients aged 18 years and older with metastatic soft-tissue sarcomas, an Eastern Cooperative Oncology Group performance status of 0–2, and who had previously received treatment with anthracycline and ifosfamide were randomly assigned (1:1) to intravenous infusion of ombrabulin 25 mg/m2 plus cisplatin 75 mg/m2 or intravenous infusion of placebo plus cisplatin 75 mg/m2 every 3 weeks. Patients were allocated to treatment using a permuted blocks randomisation scheme (block size of four) via an interactive voice-response system, and stratified by histological subtype. Patients, medical staff, study investigators, and individuals who handled and analysed the data were masked to treatment assignment. Our primary endpoint was median progression-free survival in the intention-to-treat population. Safety analyses were done on all randomised patients who received at least one dose of study drug. This trial is now closed, and is registered with ClinicalTrials.gov, number NCT00699517. Between June 13, 2008, and April 26, 2012, we randomly assigned 355 patients to ombrabulin plus cisplatin (n=176) or placebo plus cisplatin (n=179). Median duration of follow-up was 27·9 (IQR 20·9–33·2) in the placebo group and 30·5 months (20·7–37·6) in the ombrabulin group. Progression-free survival was slightly, but significantly, improved in the ombrabulin group compared with the placebo group (median 1·54 months [95% CI 1·45–2·69] vs 1·41 [1·38–1·58] months; hazard ratio 0·76 [95% CI 0·59–0·98]; p=0·0302). Grade 3 or 4 adverse events occurred more frequently in individuals in the ombrabulin group than in those in the placebo group and included neutropenia (34 [19%] in the ombrabulin group vs 14 [8%] in the placebo group) and thrombocytopenia (15 [8%] vs six [3%] for placebo). Adverse events leading to death occurred in 18 patients in the ombrabulin group and 10 patients in the placebo group. The combination of ombrabulin and cisplatin significantly improved progression-free survival; however, it did not show a sufficient clinical benefit in patients with advanced soft-tissue sarcomas to support its use as a therapeutic option. Predictive biomarkers are needed for the rational clinical development of tumour vascular-disrupting drugs for soft-tissue sarcomas. Sanofi.

Assuming that human exposure to BSE was through beef mechanically recovered meat (MRM) consumed as burgers and other meat products, we estimated the French consumption of different food items containing beef MRM, and compared these consumptions for French and British populations. To estimate consumption of meat products containing bovine MRM, we used dietary data from national individual and household food surveys conducted between 1980 and 1995. After reconciliation of consumption data between the available surveys and calendar year adjustments, we simulated consumption of one-thousandth of the French population. Consumption was estimated by birth cohort and gender, and for the periods 1980-89 and 1990-95 separately. Data showed that burgers (including manufactured minced meat) represented around 75-80% of the individual consumption of meat products containing MRM, and that consumption of burgers increased by 40% over the 1980-95 period. In all age groups, consumption was higher in males than in females. In both genders, the 1940-69 birth cohort had the highest mean consumption of burgers and other beef products containing MRM. Similar findings have been reported for the UK population. Estimated consumption of bovine MRM per calendar year increased markedly over the study period, concomitantly with an increase of bovine carcasses imported from the UK. Comparison of the 1980-1995 pattern of bovine MRM consumption in the UK and France indicated that this consumption peaked later in France than in the UK. This difference might result in different temporal pattern of vCJD incidence.

Background: This open-label, randomized phase III trial evaluated larotaxel/cisplatin versus gemcitabine/cisplatin as first-line treatment for locally advanced (T4b) or metastatic urothelial tract or bladder cancer. Methods: Patients were randomized to larotaxel 50 mg/m 2 with cisplatin 75 mg/m 2 every 3 weeks (larotaxel/cisplatin) or gemcitabine 1,000 mg/m 2 on days 1, 8, and 15 with cisplatin 70 mg/m 2 on day 1 every 4 weeks (gemcitabine/cisplatin). The primary endpoint was overall survival (OS). Results: The trial was prematurely closed following the sponsor's decision to stop clinical development of larotaxel (n = 337 randomized). The larotaxel dose was reduced to 40 mg/m 2 and cisplatin to 60 mg/m 2 following a data monitoring committee safety review of the first 97 patients. At the time of analysis, the median OS was 13.7 months [95% confidence interval (CI) 11.2-17.1] with larotaxel/cisplatin and 14.3 months (95% CI 10.5 to not reached) with gemcitabine/cisplatin [hazard ratio (HR) 1.21; 95% CI 0.83-1.76; p = 0.33]. The median progression-free survival (PFS) was 5.6 months (95% CI 4.1-6.2) with larotaxel/cisplatin and 7.6 months (95% CI 6.6-9.1) with gemcitabine/cisplatin (HR 1.67; 95% CI 1.24-2.25). More myelosuppression was observed with gemcitabine/cisplatin. Conclusion: There was no difference in OS. Although the trial was closed prematurely, PFS appeared worse with larotaxel/cisplatin, suggesting that larotaxel/cisplatin does not improve outcomes versus cisplatin/gemcitabine.