To what extent are European rules complied with, and what are the reasons for non-compliance with EU law? According to an intergovernmentalist perspective, implementation problems should occur when ...member states failed to assert their interests in the European decision-making process. Focusing on 26 infringement procedures from the area of labour law, we show that such 'opposition through the backdoor' does occur occasionally. However, we demonstrate that opposition at the end of the EU policy process may also arise without prior opposition at the beginning. Additionally, our findings indicate that non-compliance is often unrelated to opposition, and due to administrative shortcomings, interpretation problems, and issue linkage. This study is based on unique in-depth data stemming from a ground-level analysis of the implementation of six EU Directives in all 15 member states.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
The prognostic and predictive value of carbohydrate antigen 19-9 (CA 19-9) in locally advanced pancreatic cancer (LAPC) has not yet been defined from prospective randomized controlled trials (RCTs).
...A total of 165 LAPC patients were treated within the NEOLAP RCT for 16 weeks with multiagent induction chemotherapy ICT; either nab-paclitaxel/gemcitabine alone or nab-paclitaxel/gemcitabine followed by FOLFIRINOX (combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin) followed by surgical exploration of all patients without evidence of disease progression. CA 19-9 was determined at baseline and after ICT and correlated with overall survival (OS) and secondary R0 resection rate.
From the NEOLAP study population (N = 165) 133 patients (81%) were evaluable for CA 19-9 at baseline and 81/88 patients (92%) for post-ICT CA 19-9 response. Median OS (mOS) in the CA 19-9 cohort (n = 133) was 16.2 months 95% confidence interval (CI) 13.0-19.4 and R0 resection (n = 31; 23%) was associated with a significant survival benefit 40.8 months (95% CI 21.7-59.8), while R1 resected patients (n = 14; 11%) had no survival benefit 14.0 (95% CI 11.7-16.3) months, hazard ratio (HR) 0.27; P = 0.001. After ICT most patients showed a CA 19-9 response (median change from baseline: –82%; relative decrease ≥55%: 83%; absolute decrease to ≤50 U/ml: 43%). Robust CA 19-9 response (decrease to ≤50U/ml) was significantly associated with mOS 27.8 (95% CI 18.4-37.2) versus 16.5 (95% CI 11.7-21.2) months, HR 0.49; P = 0.013, whereas CA 19-9 baseline levels were not prognostic for OS. Multivariate analysis demonstrated that a robust CA 19-9 response was an independent predictive factor for R0 resection. Using a CA 19-9 decrease to ≤61 U/ml as optimal cut-off (by receiver operating characteristic analysis) yielded 72% sensitivity and 62% specificity for successful R0 resection, whereas CA 19-9 nonresponders (<20% decrease or increase) had no chance for successful R0 resection.
CA 19-9 response after multiagent ICT provides relevant prognostic and predictive information and is useful in selecting LAPC patients for explorative surgery.
ClinicalTrials.govNCT02125136; https://clinicaltrials.gov/ct2/show/NCT02125136; EudraCT 2013-004796-12; https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004796-12/results
•NEOLAP is the first prospective surgically explored LAPC cohort, evaluable for prognostic and predictive value of CA 19-9.•After multiagent ICT, R0 but not R1 resection is associated with a significant survival benefit.•Robust CA 19-9 response, but not CA 19-9 baseline level, correlates with significant OS benefit.•Robust CA 19-9 response predicts R0 resection and can guide patient selection for explorative surgery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the ...urothelium.
Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m
days 1, 8, and 15; cisplatin 70 mg/m
day 2) or standard MVAC every 28 days for a maximum of six cycles.
Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio HR, 1.04; 95% confidence interval CI, 0.82 to 1.32;
= .75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI, 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More GC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27%
18%, respectively) and thrombocytopenia (57%
21%, respectively). On both arms, the RBC transfusion rate was 13 of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate was four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82%
71%, respectively), neutropenic fever (14%
2%, respectively), neutropenic sepsis (12%
1%, respectively), and grade 3/4 mucositis (22%
1%, respectively) and alopecia (55%
11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue.
GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.
The optimal preoperative treatment for LAPC is unknown. This first prospective, randomised trial was designed to compare the efficacy and safety of nab-Paclitaxel and Gemcitabine (nPG) with ...Fluorouracil, Leucovorin, Irinotecan, Oxaliplatin (FOLFIRINOX) as induction chemotherapy in LAPC.
In this open-label, randomised, two-arm, phase 2 trial, treatment-naive patients (pts) with histologically/cytologically proven non-resectable LAPC were recruited from 33 German centres. After two cycles of nPG induction pts without progressive disease or unacceptable adverse events were randomly allocated (1:1) to receive either two additional cycles of nPG or four cycles of sequential un-modified sqFOLFIRINOX. Secondary resectability was assessed by surgical exploration in all pts with at least stable disease (SD) after completion of induction chemotherapy. The primary endpoint was conversion rate (R0/R1 resection). Secondary endpoints included overall survival (OS) and safety.
168 pts were registered and 130 were randomly allocated (64 to nPG and 66 to sqFOLFIRINOX). Disease control rate (DCR) after randomization was 82.3% in the nPG group and 75.0% % in the sqFOLFIRINOX group. Surgical exploration was performed in 62.5% of randomized pts in the nPG group and 63.6% in the sqFOLFIRINOX group. The conversion rate as primary endpoint was 30.6% in the nPG group and 45.0% in the sqFOLFIRINOX group (Odds ratio 0.54; 95% CI, 0.26 to 1.13; P=0.135). At a median follow-up of 12.9 months, the median overall survival was 17.2 months in the nPG group and 22.5 months in the sqFOLFIRINOX group (adjusted Hazard ratio 0.73; 95% CI, 0.42 to 1.28; P=0.268). Among all intention-to-treat pts (N=165) conversion was associated with significant improved overall survival (27.4 vs. 14.2 months; P=0.0035). Adverse events of ≥ grade 3 occurred in 54.7% of the patients in the the nPG group and in 53.0% of those in the in the sqFOLFIRINOX group.
Secondary resection after 4 months of induction combination chemotherapy followed by surgical exploration is feasible in about a third of pts with LAPC and associated with prolonged survival.
NCT02125136; 2013-004796-12.
AIO-Studien-gGmbH.
Celgene.
V. Kunzmann: Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (institution): Servier; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. H. Algül: Honoraria (self): Celgene; Honoraria (self): Servier; Research grant / Funding (self): Chugai. E. Goekkurt: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Travel / Accommodation / Expenses: Servier. U.M. Martens: Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy: Roche. D. Waldschmidt: Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene. U. Pelzer: Advisory / Consultancy, Research grant / Funding (institution): Celgene. J. Siveke: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Celgene; Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Roche. F. Kullmann: Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene. S. Boeck: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene. T.J. Ettrich: Research grant / Funding (institution): Shire; Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Travel / Accommodation / Expenses: Ipsen. All other authors have declared no conflicts of interest.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
RésuméLes États-nations étant attachés à leurs prérogatives en matière de politiques relatives aux personnes âgées, on pourrait en déduire que ces politiques se prêtent peu à un traitement au niveau ...supranational. Pourtant, un certain nombre d’instruments communautaires influent directement ou indirectement sur les politiques nationales conduites dans ce domaine. Alors que la recherche en sciences politiques s’intéresse essentiellement à la méthode ouverte de coordination (MOC) sur les retraites, nous montrons que ces instruments sont en réalité plus anciens, plus larges et plus influents que la MOC. Nous nous plaçons dans une perspective d’analyse des politiques et posons les questions suivantes : quand et comment ces instruments ont-ils été élaborés ? Quels sont leurs effets (potentiels) ? Nous démontrons que l’on surestime en général la puissance des instruments de pilotage non contraignants qui visent à impulser des réformes dans le domaine des retraites tandis que l’on sous-estime souvent l’influence qu’exerce l’Union européenne sur la marge de manœuvre des États en matière de vieillissement et de retraite, à travers les instruments législatifs relatifs aux droits individuels à l’égalité de traitement ou à la liberté de mouvement des capitaux et des personnes. L’analyse fait appel à des études de cas portant sur différents instruments d’action et repose sur vingt-six entretiens et sur l’étude de sources primaires et secondaires.
Nation states keep a firm grip on old age policies, they may be considered among the least likely issues to be dealt with at the supranational level. Yet, a number of community policies directly and ...indirectly exert influence on national old age policies. While the political science literature primarily focuses the OMC pensions the paper shows that these instruments are older, wider and more influential. Employing a policy analysis perspective the paper asks: When and how did these instruments develop? What are their (potential) effects? On this basis it is shown that the governance capacity of soft steering instruments, seeking to trigger reforms in the area of pensions is typically overvalued. In contrast we tend to underestimate how much the EU forms national room of manoeuvre on ageing and old age security through legislative instruments establishing individual rights for equal treatment or through the free movement of capital and persons. The analysis draws on a number of case studies on different policy instruments and is based on 26 interviews, primary and secondary document analysis. //ABSTRACT IN FRENCH: Les États-nations étant attachés à leurs prérogatives en matière de politiques relatives aux personnes âgées, on pourrait en déduire que ces politiques se prêtent peu à un traitement au niveau supranational. Pourtant, un certain nombre dinstruments communautaires influent directement ou indirectement sur les politiques nationales conduites dans ce domaine. Alors que la recherche en sciences politiques sintéresse essentiellement à la méthode ouverte de coordination (MOC) sur les retraites, nous montrons que ces instruments sont en réalité plus anciens, plus larges et plus influents que la MOC. Nous nous plaçons dans une perspective d'analyse des politiques et posons les questions suivantes : quand et comment ces instruments ont-ils été élaborés ? Quels sont leurs effets (potentiels) ? Nous démontrons que l'on surestime en général la puissance des instruments de pilotage non contraignants qui visent à impulser des réformes dans le domaine des retraites tandis que lon sous-estime souvent l'influence qu'exerce l'Union européenne sur la marge de manoeuvre des États en matière de vieillissement et de retraite, à travers les instruments législatifs relatifs aux droits individuels à légalité de traitement ou à la liberté de mouvement des capitaux et des personnes. l'analyse fait appel à des études de cas portant sur différents instruments d'action et repose sur vingt-six entretiens et sur L'étude de sources primaires et secondaires. Reproduced by permission of Bibliothèque de Sciences Po
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