Rivaroxaban thromboprophylaxis in ambulatory patients with pancreatic cancer: Results from a pre‐specified subgroup analysis of the randomized CASSINI study

Vadhan‐Raj, Saroj; McNamara, Mairéad G.; Venerito, Marino; Riess, Hanno; O'Reilly, Eileen Mary; Overman, Michael J.; Zhou, Xiao; Vijapurkar, Ujjwala; Kaul, Simrati; Wildgoose, Peter; Khorana, Alok A.

doi:10.1002/cam4.3269

Cited by 22 publications

(30 citation statements)

References 18 publications

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“…A total of 2156 records were identified through database searching. After title and abstract screening, 6 studies were assessed for eligibility [25,26,[29][30][31][32][33]. One study did not report data separately from the subgroup of PC patients [33].…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

“…One study did not report data separately from the subgroup of PC patients [33]. Finally, 5 studies meeting the inclusion criteria were included in the meta-analysis ( Figure S1) [25,26,[29][30][31][32]. The agreement between reviewers for study selection was 100% (kappa statistic 1.0), and no further resolution by a third reviewer was required.…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

“…Two dedicated open-label phase IIb RCTs (FRAGEM [25] and CONKO-004 [26]) evaluated the efficacy and safety of primary thromboprophylaxis with either dalteparin at therapeutic doses (dalteparin 200 International Units [IU]/kg once daily for 4 weeks, followed 150 IU/kg) [25] or enoxaparin at supra-prophylactic doses (enoxaparin 1 mg/kg once daily) [26] in ambulatory patients with advanced PC receiving chemotherapy, with no treatment as a comparator. Three double-blinded placebo-controlled phase III RCTs evaluated the efficacy and safety of primary thromboprophylaxis with prophylactic doses of nadroparin (3800 IU once daily, PROTECHT trial [31]) or semuloparin (20 mg once daily, SAVE-ONCO trial [32]) or rivaroxaban (10 mg once daily, CASSINI trial [29,30]) in ambulatory patients with various cancer types receiving chemotherapy and reported data from a subgroup of PC patients. Duration of thromboprophylaxis ranged from 3 to 6 months (Table 1).…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

“…Recently, the CASSINI trial assessed the efficacy and safety of prophylactic doses of rivaroxaban for preventing VTE in ambulatory cancer patients receiving systemic anticancer therapy who were at intermediate-to-high-risk of VTE (Khorana score ≥ 2 prior to starting chemotherapy) [29]. A subgroup analysis of PC patients included in the CASSINI phase III trial was subsequently released [29,30]. This subgroup analysis increases the size and quality of the dataset available for a meta-analysis assessing the efficacy and safety of anticoagulants for primary thromboprophylaxis in PC patients.…”

Section: Introductionmentioning

confidence: 99%

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Primary Thromboprophylaxis in Ambulatory Pancreatic Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Frère

Crichi

Bournet

et al. 2020

Cancers

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Patients with pancreatic cancer (PC) carry the highest risk of venous thromboembolism (VTE) amongst all cancer patients. Appropriate use of primary thromboprophylaxis might significantly and safely reduce its burden. We performed a systematic review of published studies and meeting abstracts using MEDLINE and EMBASE through July 2020 to evaluate the efficacy and safety of primary thromboprophylaxis in ambulatory PC patients receiving chemotherapy. The Mantel–Haenszel random effect model was used to estimate the pooled event-based risk ratio (RR) and the pooled absolute risk difference (RD) with a 95% confidence interval (CI). Five randomized controlled studies with 1003 PC patients were included in this meta-analysis. Compared to placebo, thromboprophylaxis significantly decreased the risk of VTE (pooled RR 0.31, 95% CI 0.19–0.51, p < 0.00001, I2 = 8%; absolute RD −0.08, 95% CI −0.12–−0.05, p < 0.00001, I2 = 0%), with an estimated number needed to treat of 11.9 patients to prevent one VTE event. Similar reductions of VTE were observed in studies with parenteral (RR 0.30, 95% CI 0.17–0.53) versus oral anticoagulants (RR 0.37, 95% CI 0.14–0.99) and in studies using prophylactic doses of anticoagulants (RR 0.34, 95% CI 0.17–0.70) versus supra-prophylactic doses of anticoagulants (RR 0.27, 95% CI 0.08–0.90). The pooled RR for major bleeding was 1.08 (95% CI 0.47–2.52, p = 0.85, I2 = 0%) and the absolute RD was 0.00 (95% CI −0.02–0.03, p = 0.85, I2 = 0%). Evidence supports a net clinical benefit of thromboprophylaxis in ambulatory PC patients receiving chemotherapy. Adequately powered randomized phase III studies assessing the most effective anticoagulant and the optimal dose, schedule and duration of thromboprophylaxis to be used are warranted.

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Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Primary Thromboprophylaxis in Ambulatory Pancreatic Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Frère

Crichi

Bournet

et al. 2020

Cancers

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“…In this Special Issue of Cancers , results from a meta-analysis pooling data from 1003 PC patients included in five RCTs comparing pharmacological thromboprophylaxis to placebo or no placebo control for VTE prevention demonstrated that primary thromboprophylaxis decreases the risk of VTE by 69%, without increase in the risk of major bleeding [ 16 ]. This systematic review and meta-analysis included data from a subgroup of PC patients enrolled in a DOAC placebo-controlled trial for primary VTE prevention [ 27 ]. The results support the most recent ITAC [ 5 ] and ASCO [ 6 ] guidelines that recommend primary prophylaxis using either LMWH or DOAC for all ambulatory PC patient receiving systemic anticancer therapy and with a low risk of bleeding.…”

mentioning

confidence: 99%

Management of Cancer-Associated Thrombosis: An Evolving Area

Frère

Connors

Farge

2020

Cancers

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The management of cancer-associated thrombosis (CAT) is an evolving area. With the use of direct oral anticoagulants as a new option in the management of CAT, clinicians now face several choices for the individual cancer patient with venous thromboembolism. A personalized approach, matching the right drug to the right patient, based on drug properties, efficacy and safety, side effect profile of each drug, and patient values and preference, will probably supplant the one size fits all approach of use of only low-molecular-weight heparin in the near future. We herein present eight translational, clinical research, and review articles on recent advances in the management of CAT published in the Special Issue “Treatment for Cancer-Associated Thrombosis” of Cancers. For now, a multidisciplinary patient-centered approach involving a close cooperation between oncologists and other specialists is warranted to guide clinical decision making and optimize the treatment of VTE in cancer patient.

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Risk-Directed Ambulatory Thromboprophylaxis in Lung and Gastrointestinal Cancers

Alexander,

Harris,

Underhill

et al. 2023

JAMA Oncol

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ImportanceThromboprophylaxis for individuals receiving systemic anticancer therapies has proven to be effective. Potential to maximize benefits relies on improved risk-directed strategies, but existing risk models underperform in cohorts with lung and gastrointestinal cancers.ObjectiveTo assess clinical benefits and safety of biomarker-driven thromboprophylaxis and to externally validate a biomarker thrombosis risk assessment model for individuals with lung and gastrointestinal cancers.Design, Setting, and ParticipantsThis open-label, phase 3 randomized clinical trial (Targeted Thromboprophylaxis in Ambulatory Patients Receiving Anticancer Therapies [TARGET-TP]) conducted from June 2018 to July 2021 (with 6-month primary follow-up) included adults aged 18 years or older commencing systemic anticancer therapies for lung or gastrointestinal cancers at 1 metropolitan and 4 regional hospitals in Australia. Thromboembolism risk assessment based on fibrinogen and d-dimer levels stratified individuals into low-risk (observation) and high-risk (randomized) cohorts.InterventionsHigh-risk patients were randomized 1:1 to receive enoxaparin, 40 mg, subcutaneously daily for 90 days (extending up to 180 days according to ongoing risk) or no thromboprophylaxis (control).Main Outcomes and MeasuresThe primary outcome was objectively confirmed thromboembolism at 180 days. Key secondary outcomes included bleeding, survival, and risk model validation.ResultsOf 782 eligible adults, 328 (42%) were enrolled in the trial (median age, 65 years [range, 30-88 years]; 176 male [54%]). Of these participants, 201 (61%) had gastrointestinal cancer, 127 (39%) had lung cancer, and 132 (40%) had metastatic disease; 200 (61%) were high risk (100 in each group), and 128 (39%) were low risk. In the high-risk cohort, thromboembolism occurred in 8 individuals randomized to enoxaparin (8%) and 23 control individuals (23%) (hazard ratio [HR], 0.31; 95% CI, 0.15-0.70; P = .005; number needed to treat, 6.7). Thromboembolism occurred in 10 low-risk individuals (8%) (high-risk control vs low risk: HR, 3.33; 95% CI, 1.58-6.99; P = .002). Risk model sensitivity was 70%, and specificity was 61%. The rate of major bleeding was low, occurring in 1 participant randomized to enoxaparin (1%), 2 in the high-risk control group (2%), and 3 in the low-risk group (2%) (P = .88). Six-month mortality was 13% in the enoxaparin group vs 26% in the high-risk control group (HR, 0.48; 95% CI, 0.24-0.93; P = .03) and 7% in the low-risk group (vs high-risk control: HR, 4.71; 95% CI, 2.13-10.42; P &lt; .001).Conclusions and RelevanceIn this randomized clinical trial of individuals with lung and gastrointestinal cancers who were stratified by risk score according to thrombosis risk, risk-directed thromboprophylaxis reduced thromboembolism with a desirable number needed to treat, without safety concerns, and with reduced mortality. Individuals at low risk avoided unnecessary intervention. The findings suggest that biomarker-driven, risk-directed primary thromboprophylaxis is an appropriate approach in this population.Trial RegistrationANZCTR Identifier: ACTRN12618000811202

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Rivaroxaban thromboprophylaxis in ambulatory patients with pancreatic cancer: Results from a pre‐specified subgroup analysis of the randomized CASSINI study

Cited by 22 publications

References 18 publications

Primary Thromboprophylaxis in Ambulatory Pancreatic Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Primary Thromboprophylaxis in Ambulatory Pancreatic Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Management of Cancer-Associated Thrombosis: An Evolving Area

Risk-Directed Ambulatory Thromboprophylaxis in Lung and Gastrointestinal Cancers

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