Efficacy and Safety of Tinzaparin in CAT Patients with Metastatic Disease
Notice bibliographique
Résumé
Introduction Venous thromboembolism (VTE) frequently complicates the course of active cancer with a significant impact on morbidity and mortality. The results of CATCH trial for treatment of cancer-associated thrombosis (CAT) have been reported and included patients with and without metastatic disease. As metastatic disease is known to be associated with a higher risk of recurrent VTE and bleeding, we performed these post hoc analyses to assess the recurrent VTE (rVTE), recurrent deep vein thrombosis (rDVT), and bleeding events (major bleeding (MB), clinically relevant (CRB) and clinically relevant non-major (CRNMB)) in patients with CAT with metastatic disease. Risk factors associated with rVTE, rDVT and CRB were also explored. Method CATCH (ClinicalTrials.govNCT01130025; Lee A et al. JAMA 2015) was a Phase III, multinational, randomized, active-controlled, open-label trial. Patients with solid tumor cancer and haematological malignancies were included. Patients were randomized to receive therapeutic dosing of tinzaparin (175 U/kg OD) vs warfarin (INR target 2.0 - 3.0). Treatment was given for up to 6 months. The primary efficacy outcome was the composite of symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), fatal PE, incidental proximal DVT and incidental proximal PE. All cumulative incidence VTE and MB outcome were objectively documented and centrally adjudicated in a treatment-blinded fashion. Patients who had known metastatic solid tumor at presentation were included in these analysis. The regression model compared the two treatment groups adjusting for competing risks and geographical region and history of VTE. Results Among the CATCH study population, 55% had metastatic disease. Of these patients, 247 and 245 received tinzaparin and warfarin, respectively, with no significant differences in patient characteristics between treatment groups. Patients with metastatic disease had a higher incidence of rVTE (10.2% vs 7.0%) and symptomatic non-fatal rDVT (5.5% vs 2.9%) compared to patients without metastatic disease. Patients with metastatic disease also had a higher incidence of MB (2.8% vs 1.9%), CRB (17.7%% vs 11.8%) and CRNMB (15.0% vs 10.5%) compared to patients without metastatic disease. rVTE occurred in significantly fewer patients assigned to tinzaparin (6.8%) versus warfarin (14.4%) (HR 0.45; 95%CI 0.25-0.80; p=0.007). rDVT also occurred significantly less frequently in patients assigned to tinzaparin (3.0%) versus warfarin (8.4%) (HR 0.34; 95%CI 0.15-0.81; p=0.015). 96% of rVTE were symptomatic. There was no significant difference in MB between tinzaparin- and warfarin-treated patients (4.0% vs 1.6%; HR 2.17; 95%CI 0.71-6.65; p=0.177), but tinzaparin was associated with significantly lower risk of CRB (15.8% vs 19.6%; HR 0.63; 95%CI 0.41-0.97; p=0.037) and CRNMB (12.1% vs 18.0%; HR 0.53; 95%CI 0.33-0.84; p=0.008). Factors associated with rVTE in patients with metastatic disease included central venous catheterization (HR 0.10; 95%CI 0.01-0.79; p=0.029), venous compression from mass or adenopathy (HR 3.99; 95%CI 2.14-7.43; p<0.001), and hepatobiliary cancer (HR 4.07; 95%CI 1.65-10.0; p=0.002). The latter two were also significant risk factors for rDVT. Age > 75 (HR 2.56; 95%CI 1.43-4.60; p=0.002) and known intracranial pathology (HR 2.24; 95%CI 1.07-4.66; p=0.031) were found to be significant risk factors for CRB. Conclusion CAT patients with metastatic diseases have higher risks of rVTE and bleeding compared with patients without metastases. Amongst CAT patients with metastatic solid tumors, treatment with tinzaparin was associated with significantly lower risk of rVTE and rDVT and significantly lower risk of CRB and CRNMB compared with warfarin. Tinzaparin offers a favourable risk-benefit profile in treatment of CAT in patients with metastatic solid tumors. Disclosures Lee: Pfizer: Consultancy, Honoraria; BMS: Research Funding; LEO Pharma A/S: Consultancy, Honoraria; Bayer: Consultancy, Honoraria, Other: Advisory board, steering committee. Bauersachs:Aspen: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; LEO Pharma A/S: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Turpin:LEO Pharma Canada: Current Employment. Hansen:LEO Pharma A/S: Current Employment. Khorana:Leo Pharma: Honoraria; Merck: Research Funding; Array: Other: Research funding (to institution); Leap: Research Funding; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Janssen: Honoraria; Pfizer: Honoraria; Medscape: Honoraria; Bayer: Honoraria; BMS: Honoraria, Research Funding; Sanofi: Honoraria.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».