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SELECT-D

Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D)

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Year of Publication: 2018

Authors: Annie M. Young, Andrea Marshall, Jenny Thirlwall, ..., Mark Levine

Journal: Journal of Clinical Oncology

Link: https://doi.org/10.1200/JCO.2018.78.8034

Clinical Question

Is rivaroxaban an effective alternative to dalteparin for treatment of VTE in patients with cancer?

Bottom Line

Rivaroxaban was associated with lower VTE recurrence but higher clinically relevant non-major bleeding compared with dalteparin in cancer patients

        Major Points
        Multicenter, randomized, open-label pilot trial in cancer patients with VTE
Rivaroxaban significantly reduced VTE recurrence (4% vs 11%, HR 0.43)
Major bleeding rates were similar between groups (6% vs 4%)
Rivaroxaban increased clinically relevant non-major bleeding (13% vs 4%, HR 3.76)
58% of patients had metastatic disease
Most bleeding events were gastrointestinal
Esophageal/gastroesophageal cancers excluded during trial due to bleeding concerns

      

Design

Study Type: Multicenter, randomized, open-label pilot trial

Randomization: 1

Blinding: Open-label (no blinding)

Enrollment Period: September 6, 2013 to December 22, 2016

Follow-up Duration: 6 months

Centers: 58

Countries: United Kingdom

Sample Size: 406

Analysis: Intention-to-treat analysis using Kaplan-Meier estimates and Cox models for hazard ratios

Inclusion Criteria

Active cancer (solid and hematologic malignancies)
Primary objectively confirmed VTE (symptomatic lower-extremity proximal DVT, symptomatic PE, or incidental PE)
Age ≥18 years
Weight ≥40 kg
Eastern Cooperative Oncology Group performance status ≤2
Adequate hematologic, hepatic, and renal function

Exclusion Criteria

Previous treatment dose of anticoagulant or >75 mg aspirin per day
History of VTE
Clinically significant liver disease
Bacterial endocarditis
Active bleeding or high risk of bleeding
Uncontrolled hypertension
Inadequate contraceptive measures if of childbearing potential
Concomitant use of strong cytochrome P-450 3A4 inhibitors or inducers
P-glycoprotein inhibitors or inducers

Arms

Field	Control	Rivaroxaban
Intervention	Dalteparin 200 IU/kg subcutaneously once daily for month 1, then 150 IU/kg subcutaneously once daily for months 2-6	Rivaroxaban 15 mg orally twice daily for 3 weeks, then 20 mg once daily for total of 6 months
Duration	6 months	6 months

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR
VTE recurrence over 6 months	Primary	11% (95% CI, 7% to 16%)	4% (95% CI, 2% to 9%)	0.43
Major bleeding at 6 months	Secondary	4% (95% CI, 2% to 8%)	6% (95% CI, 3% to 11%)	1.83
Clinically relevant non-major bleeding at 6 months	Secondary	4% (95% CI, 2% to 9%)	13% (95% CI, 9% to 19%)	3.76
Overall survival at 6 months	Secondary	70% (95% CI, 63% to 76%)	75% (95% CI, 69% to 81%)
Major bleeding	Adverse	6 patients	11 patients	1.83
CRNMB	Adverse	7 patients	25 patients	3.76

Subgroup Analysis

Site of primary tumor (stomach/pancreas vs other; lung/lymphoma/gynecologic/bladder vs other) and VTE type (symptomatic VTE vs incidental PE) predicted VTE recurrence. Patients with esophageal/gastroesophageal cancer had higher bleeding risk with rivaroxaban

Criticisms

Open-label design may introduce bias
Recruitment was slower than anticipated
Second randomization component was closed early due to futility
Sample size was reduced during the trial
High mortality rate affected completion of 6-month treatment
Results may not be generalizable to longer treatment durations
Imbalance in incidental PE detection between arms may have affected results

Funding

Supported by an unrestricted educational grant from Bayer AG, which also provided rivaroxaban and placebo tablets

Based on: SELECT-D (Journal of Clinical Oncology, 2018)

Authors: Annie M. Young, Andrea Marshall, Jenny Thirlwall, ..., Mark Levine

Content summarized and formatted by NeuroTrials.ai.

SELECT-D

(2018)

Objective

To assess if rivaroxaban would offer an alternative treatment for VTE in patients with cancer compared to dalteparin

Study Summary

• Rivaroxaban reduced VTE recurrence compared to dalteparin (4% vs 11%, HR 0.43)
• Rivaroxaban increased clinically relevant non-major bleeding (13% vs 4%, HR 3.76)
• Major bleeding was similar between groups (6% vs 4%)

Intervention

Rivaroxaban vs dalteparin for 6 months

Inclusion Criteria

Active cancer patients with symptomatic PE, incidental PE, or symptomatic lower-extremity proximal DVT

Study Design

Arms: Rivaroxaban (15mg BID x 3 weeks, then 20mg daily) vs Dalteparin (200 IU/kg daily month 1, then 150 IU/kg daily months 2-6)

Patients per Arm: 203 per arm

Outcome

• Primary: VTE recurrence over 6 months
• Secondary: Major bleeding and clinically relevant non-major bleeding
• Safety outcomes assessed throughout study period

Bottom Line

Rivaroxaban was associated with lower VTE recurrence but higher clinically relevant non-major bleeding compared with dalteparin in cancer patients

Major Points

Multicenter, randomized, open-label pilot trial in cancer patients with VTE
Rivaroxaban significantly reduced VTE recurrence (4% vs 11%, HR 0.43)
Major bleeding rates were similar between groups (6% vs 4%)
Rivaroxaban increased clinically relevant non-major bleeding (13% vs 4%, HR 3.76)
58% of patients had metastatic disease
Most bleeding events were gastrointestinal
Esophageal/gastroesophageal cancers excluded during trial due to bleeding concerns

Study Design

Study Type: Multicenter, randomized, open-label pilot trial
Randomization: Yes
Blinding: Open-label (no blinding)
Sample Size: 406
Follow-up: 6 months
Centers: 58
Countries: United Kingdom

Primary Outcome

Definition: VTE recurrence over 6 months

Control	Intervention	HR/OR	P-value
11% (95% CI, 7% to 16%)	4% (95% CI, 2% to 9%)	0.43 (0.19 to 0.99)

Limitations & Criticisms

Open-label design may introduce bias
Recruitment was slower than anticipated
Second randomization component was closed early due to futility
Sample size was reduced during the trial
High mortality rate affected completion of 6-month treatment
Results may not be generalizable to longer treatment durations
Imbalance in incidental PE detection between arms may have affected results

Citation

View Original Publication →

SELECT-D

Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D)

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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