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1068 Efficacy and Safety of Rivaroxaban in Patients with CAT: A Pooled Meta-Analysis of 3 Randomized Controlled Trials

Program: Oral and Poster Abstracts
Session: 332. Anticoagulation and Antithrombotic Therapies: Poster I
Hematology Disease Topics & Pathways:
Clinical Research
Saturday, December 11, 2021, 5:30 PM-7:30 PM

Silvy Laporte, PhD1*, Andrea Marshall, PhD2*, Annie Young, PhD2*, Hanno Riess3*, Marianne Sinn, MD4*, Philippe Girard, MD5* and Olivier Sanchez6*

1Clinical Pharmacology Unit, University Hospital of Saint-Etienne, INSERM U-1059 and F-CRIN INNOVTE network, France, Saint- Etienne, France
2Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, United Kingdom
3Hematology, Oncology, and Tumorimmunology, Charité Universitätsmedizin Berlin, Berlin, Germany
4Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
5Département de Pneumologie, Institut du thorax Curie-Montsouris, Paris and F-CRIN INNOVTE network, France, Paris, FRA
6Service de pneumologie, Hôpital Européen Georges Pompidou, Paris and F-CRIN INNOVTE network, France, Paris, France

Introduction: CALLISTO, a comprehensive programme of research on cancer-associated thrombosis (CAT), included 3 randomized trials of rivaroxaban versus low molecular weight heparin (LMWH) for the treatment of venous thrombosis in patients with solid and haematological cancers (SELECT-D, CASTA-DIVA and CONKO-11). A meta-analysis of these studies was conducted to improve the precision of current estimates of the efficacy and safety of rivaroxaban in this patient group and investigate how patient characteristics impact the treatment effects.

Methods: The primary endpoint was the cumulative incidence of venous thromboembolism (VTE) recurrence at the end of the treatment period (≥3 months). Other endpoints included major bleeding (MB), a composite of MB or clinically relevant non-major bleeding (clinically relevant bleeding [CRB]) and deaths from any cause. All endpoints were assessed by 8 pre-defined subgroup analyses: age, gender, creatinine clearance, type of index VTE, index VTE localization, cancer localization, performance status and presence of metastases (Prospero submission 266227). Patient-level data were used in this analysis.

The cumulative incidences of VTE recurrence, CRB were estimated using the Kalbfleisch and Prentice model, while the Kaplan-Meier model was used to estimate the incidence of death. Comparisons between rivaroxaban and LMWH for VTE recurrence, MB and CRB were assessed by sub-distribution hazard ratios (SubHR) and 95% confidence intervals (CI), whereas hazard ratios and 95% CIs were used for the all-cause death endpoint. The pooled treatment effect size of each study was estimated using fixed-effect and random-effects models.

Results: When considering the prevention of VTE recurrence in the 3 randomized trials (N=804), an overall reduction of 48% was observed with rivaroxaban compared with LMWH (SubHR = 0.52, 95% CI 0.28─0.98). The estimation appeared to be homogeneous across subgroups of patients. In comparison with LMWH, rivaroxaban was associated with an increased risk of CRB (SubHR = 2.03, 95% CI 1.34─3.09), without significant difference in MB (SubHR = 1.24, 95% CI 0.60─2.57), and no difference was observed for death.

Conclusions: This pooled analysis suggests that rivaroxaban may be an alternative treatment option for the prevention of VTE recurrence in cancer patients with VTE. The gain in statistical power has shown significant benefit, as well as some risk associated with rivaroxaban treatment in this complex patient population. The impact of patient characteristics on these treatment effects will be presented at the meeting.

Disclosures: Laporte: Bayer Healthcare: Other: personal fees and non-financial support; Pfizer: Other: non-financial support; LEO Pharma: Other: non-financial support. Marshall: Bayer: Research Funding. Young: BMS/Pfizer Alliance: Honoraria; Leo Pharma: Honoraria; Chugai: Honoraria; Bayer: Honoraria, Research Funding. Riess: Bristel Myers Squibb: Honoraria; Bayer: Honoraria, Research Funding; Daiichi Sankyo: Honoraria; ASPEN: Honoraria; Leo Pharma: Honoraria; Pfizer: Honoraria. Sinn: BMS: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Pfizer: Honoraria; Servier: Consultancy, Honoraria, Research Funding; Astra Zenica: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; MSD: Consultancy, Research Funding; Sanofi: Consultancy; Bayer: Research Funding. Girard: Bayer Healthcare: Other: Personal fees, Research Funding; LEO Pharma: Other: Perconal fees, Research Funding. Sanchez: BOSTON SCIENTIFICS: Other: grants and personal fees; CHIESI: Other: personal fees; BOEHRINGER INGELHEIM: Other: personal fees and non-financial support; PFIZER: Other: personal fees and non-financial support; BMS: Other: grants, personal fees and non-financial support; BAYER: Other: reports grants, personal fees and non-financial suppor.

*signifies non-member of ASH