Rivaroxaban for Preventing Venous Thromboembolism in High-Risk Ambulatory Patients with Cancer: Rationale and Design of the CASSINI Trial

Khorana, Alok A.; Vadhan‐Raj, Saroj; Kuderer, Nicole M.; Wun, Theodore; Liebman, Howard A.; Soff, Gerald A.; Belani, Chandra P.; O’Reilly, Eileen M.; McBane, Robert D.; Eikelboom, John W.; Damaraju, C. V.; Beyers, Karen; Dietrich, Flavia; Kakkar, Ajay K.; Riess, Hanno; Peixoto, Renata D’Alpino; Lyman, Gary H.

doi:10.1160/th17-03-0171

Cited by 57 publications

(66 citation statements)

References 58 publications

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“…To determine which patients would receive the most benefit from a preventive strategy, recent studies have used a risk‐stratified approach to study the impact of thromboprophylaxis in higher risk VTE patients based on the Khorana score . The Khorana score is a validated clinical score that stratifies patients into low‐ (0), intermediate‐ (1‐2), and high‐risk (3+) categories based on a combination of cancer and patient characteristics before chemotherapy initiation .…”

Section: Introductionmentioning

confidence: 99%

“…8 To determine which patients would receive the most benefit from a preventive strategy, recent studies have used a risk-stratified approach to study the impact of thromboprophylaxis in higher risk VTE patients based on the Khorana score. [9][10][11] The Khorana score is a validated clinical score that stratifies patients into low-(0), intermediate-(1-2), and high-risk (3+) categories based on a combination of cancer and patient characteristics before chemotherapy initiation. 12 In the current study, we report a systematic literature review and meta-analysis of phase III studies of direct oral anticoagulant (DOAC) vs placebo for the prevention of VTE in the adult, ambulatory cancer patients receiving systemic therapy.…”

Section: Introductionmentioning

confidence: 99%

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Direct oral anticoagulant for the prevention of thrombosis in ambulatory patients with cancer: A systematic review and meta‐analysis

Kuderer

García

et al. 2019

Journal of Thrombosis and Haemostasis

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Background It is unclear if direct oral anticoagulant (DOAC) is efficacious and safe for prophylaxis of venous thromboembolism (VTE) in ambulatory patients with cancer. Methods We performed a systematic review using EMBASE, MEDLINE, and CENTRAL. Inclusion criteria included adult ambulatory patients with cancer, prophylactic use of DOAC, and randomized controlled trials. Exclusion criteria included pediatric patients, inpatient or postoperative setting, therapeutic indication of DOAC, or non‐phase III randomized controlled trial. Two authors screened/reviewed articles and abstracted the data. Meta‐analysis was performed using random‐effects model. Efficacy outcome included overall and symptomatic VTE incidence during the first 6 months. Safety outcomes included major bleeding and clinically relevant non‐major bleeding (CRNMB) incidence during the on‐treatment period. Subgroup analysis was performed for intermediate‐ and high‐risk Khorana score. Results A total of 202 records were identified and 28 full‐text articles were assessed. Two studies with 1415 participants were included for meta‐analysis. For DOAC vs placebo, the relative risks for overall and symptomatic VTE incidence by 6 months were 0.56 (0.35‐0.89) and 0.58 (0.29‐1.13), respectively. The relative risks for major bleeding and CRNMB while on‐treatment were 1.96 (0.80‐4.82) and 1.28 (0.74‐2.20), respectively. Patients with high‐risk Khorana score (3+) derived the largest absolute risk reduction of VTE. Conclusions Low‐dose DOAC reduces the rate of overall VTE in higher risk cancer patients starting systemic chemotherapy. It may reduce the rate of symptomatic VTE but increase the likelihood of bleeding.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Direct oral anticoagulant for the prevention of thrombosis in ambulatory patients with cancer: A systematic review and meta‐analysis

Kuderer

García

et al. 2019

Journal of Thrombosis and Haemostasis

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“…Novel thromboprophylaxis strategies in patients with cancer and high VTE risk are currently being explored in two ongoing trials. 26,27 The effectiveness of direct oral anticoagulants is being studied in these trials and the results may offer a new approach to prevent thrombosis in patients with cancer.…”

Section: Resultsmentioning

confidence: 99%

“…Our data suggest that ACPC patients undergoing pancreatic cancer surgery have higher VTE risk in the postoperative period and extended thromboprophylaxis should be considered in these patients. Novel thromboprophylaxis strategies in patients with cancer and high VTE risk are currently being explored in two ongoing trials . The effectiveness of direct oral anticoagulants is being studied in these trials and the results may offer a new approach to prevent thrombosis in patients with cancer.…”

Section: Discussionmentioning

confidence: 99%

Postoperative venous thromboembolism and mortality in patients with pancreatic surgery

Majmudar

Quintero

Fuentes

et al. 2019

Journal of Surgical Oncology

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Background and Objectives Pancreatic cancer is strongly associated with thrombosis. We investigated early postoperative venous thromboembolism (PVTE) mortality among patients with pancreatic surgery and compared outcomes in adenocarcinoma pancreatic cancer (ACPC) to non‐adenocarcinoma pancreatic neoplasm (NACPN). Methods We analyzed a prospectively collected database of patients who underwent pancreatic cancer or neoplasm‐related surgery. As NACPN is underrepresented in other studies, we selected NACPN patients and a random sample of ACPC patients. PVTE was defined as VTE occurring within 3 months of surgical intervention. Statistical analysis was performed using Cox proportional hazards regression. Results A total of 441 pancreatic surgery patients were included, with 331 ACPC and 110 NACPN. Median follow‐up was 449 days during which 90 (20.4%) patients developed VTE. PVTE occurred in 53 (12.0%) patients, including 41 (12.4%) ACPC patients and 12 (10.9%) NACPN patients. Those with PVTE had 60% higher mortality rate. A multivariable analysis found that PVTE is an independent predictor of increased mortality (HR Adj, 1.6; 95% CI, 1.1‐2.2; P < .01). The mortality impact was not consistent between ACPC (HR, 3.2; 95% CI, 1.3‐7.9) and NACPN groups (HR, 1.3; 95% CI, 0.9‐1.8). Conclusions Postoperative venous thromboembolism is an independent predictor of increased mortality in pancreatic surgery, specifically in adenocarcinoma pancreatic cancer surgery.

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“…CASSINI was a multicenter trial, with a similar study design to AVERT, which assessed rivaroxaban versus placebo for thromboprophylaxis in ambulatory patients with cancer who initiated systemic therapy and had a Khorana risk score ≥ 2 . A major difference in the design of CASSINI versus AVERT is that CASSINI mandated lower‐extremity ultrasonography at baseline (thus excluding any inapparent deep vein thrombosis [DVT] at baseline) and serial time points during the study, and accepted on‐study screen‐detected VTE as an end point, whereas AVERT focused on symptomatic VTE only . In CASSINI, advanced pancreatic cancer status was used for stratification, as prior to the study, approximately 25% of enrolled patients were expected to have the disease (the actual proportion was 32.6% of randomized patients).…”

Section: Evidence Base For the Use Of Rivaroxaban In Catmentioning

confidence: 99%

Cancer‐associated venous thromboembolism: Treatment and prevention with rivaroxaban

Bauersachs¹,

Khorana

Lee

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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Cancer‐associated venous thromboembolism (VTE) is a frequent, potentially life‐threatening event that complicates cancer management. Anticoagulants are the cornerstone of therapy for the treatment and prevention of cancer‐associated thrombosis (CAT); factor Xa–inhibiting direct oral anticoagulants (DOACs; apixaban, edoxaban, and rivaroxaban), which have long been recommended for the treatment of VTE in patients without cancer, have been investigated in this setting. The first randomized comparisons of DOACs against low‐molecular‐weight heparin for the treatment of CAT indicated that DOACs are efficacious in this setting, with findings reflected in recent updates to published guidance on CAT treatment. However, the higher risk of bleeding events (particularly in the gastrointestinal tract) with DOACs highlights the need for appropriate patient selection. Further insights will be gained from additional studies that are ongoing or awaiting publication. The efficacy and safety of DOAC thromboprophylaxis in ambulatory patients with cancer at a high risk of VTE have also been assessed in placebo‐controlled randomized controlled trials of apixaban and rivaroxaban. Both studies showed efficacy benefits with DOACs, but both studies also showed a nonsignificant increase in major bleeding events while on treatment. This review summarizes the evidence base for rivaroxaban use in CAT, the patient profile potentially most suited to DOAC use, and ongoing controversies under investigation. We also describe ongoing studies from the CALLISTO (Cancer Associated thrombosis—expLoring soLutions for patients through Treatment and Prevention with RivarOxaban) program, which comprises several randomized clinical trials and real‐world evidence studies, including investigator‐initiated research.

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Rivaroxaban for Preventing Venous Thromboembolism in High-Risk Ambulatory Patients with Cancer: Rationale and Design of the CASSINI Trial

Cited by 57 publications

References 58 publications

Direct oral anticoagulant for the prevention of thrombosis in ambulatory patients with cancer: A systematic review and meta‐analysis

Direct oral anticoagulant for the prevention of thrombosis in ambulatory patients with cancer: A systematic review and meta‐analysis

Postoperative venous thromboembolism and mortality in patients with pancreatic surgery

Cancer‐associated venous thromboembolism: Treatment and prevention with rivaroxaban

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