Efficacy and Safety of Apixaban Thromboprophylaxis According to Baseline Chemotherapy Class in High‐Risk Ambulatory Cancer Patients: A Post Hoc Analysis of the AVERT Trial
7 affiliations
- 1Faculty of Medicine McGill University Montreal Quebec Canada
- 2Department of Medicine University of British Columbia Vancouver British Columbia Canada
- 3Department of Medicine University of Ottawa at the Ottawa Hospital Ottawa Ontario Canada
- 4Method Center The Ottawa Hospital Research Institute Ottawa Ontario Canada
- 5Department of Medicine Sault Area Hospital Sault Ste. Marie Ontario Canada
- 6Department of Medicine Nova Scotia Health, Dalhousie University Halifax Nova Scotia Canada
- 7Jewish General Hospital, Lady Davis Institute for Medical Research McGill University Montreal Quebec Canada
Abstract
Background: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. The AVERT trial showed apixaban thromboprophylaxis reduced VTE in intermediate‐to‐high‐risk patients initiating chemotherapy. However, the efficacy and safety of apixaban according to baseline chemotherapy class remain incompletely characterized.
Methods: We conducted a post hoc analysis stratified by chemotherapy class of the randomized, double‐blind, placebo‐controlled AVERT trial comparing apixaban (2.5 mg twice daily) with placebo in ambulatory cancer patients initiating chemotherapy. The primary efficacy outcome was VTE, and the primary safety outcome was clinically relevant bleeding (major or clinically relevant non major bleeding (CRNMB)) per ISTH criteria. A subgroup analysis compared platinum‐based with non‐platinum chemotherapy. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CI), adjusted for age, sex, and study site. Treatment‐by‐platinum interaction terms were used to assess effect modification by platinum exposure.
Results: A total of 563 patients were included and categorized by one or more chemotherapy classes at randomization. Compared with placebo, apixaban appeared to reduce VTE in patients on platinum (HR 0.30, 95% CI 0.16–0.57), taxane (HR 0.42, 95% CI 0.23–0.75), taxane‐platinum (HR 0.28, 95% CI 0.12–0.68), topoisomerase inhibitor (HR 0.32, 95% CI 0.19–0.53), and antimetabolite regimens (HR 0.25, 95% CI 0.12–0.54), without increased bleeding. Among placebo‐treated patients, platinum‐based chemotherapy was associated with a higher risk of VTE compared with non‐platinum regimens (HR 2.25, 95% CI 1.48–3.42), whereas no statistically significant difference was observed among apixaban‐treated patients. Treatment‐by‐platinum interaction testing did not demonstrate significant effect modification by platinum exposure.
Conclusion: In this exploratory, hypothesis‐generating analysis, apixaban thromboprophylaxis was associated with reduced VTE across several chemotherapy regimens with generally acceptable safety outcomes. Patients receiving platinum‐based chemotherapy may derive greater absolute benefit from thromboprophylaxis in the setting of higher underlying thrombotic risk.
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BibTeX
@article{feng2026efficacy,
title = {{Efficacy and Safety of Apixaban Thromboprophylaxis According to Baseline Chemotherapy Class in High‐Risk Ambulatory Cancer Patients: A Post Hoc Analysis of the AVERT Trial}},
author = {Nadia Linxi Feng and John Doering and Tzu‐Fei Wang and Ranjeeta Mallick and Grégoire Le Gal and Joseph Shaw and Danny Hill and Sudeep Shivakumar and Vicky Tagalakis and Phil Wells and Marc Carrier},
journal = {Cancer Medicine},
year = {2026},
month = oct,
doi = {10.1002/cam4.72423},
url = {https://doi.org/10.1002/cam4.72423},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Efficacy and Safety of Apixaban Thromboprophylaxis According to Baseline Chemotherapy Class in High‐Risk Ambulatory Cancer Patients: A Post Hoc Analysis of the AVERT Trial
AU - Nadia Linxi Feng
AU - John Doering
AU - Tzu‐Fei Wang
AU - Ranjeeta Mallick
AU - Grégoire Le Gal
AU - Joseph Shaw
AU - Danny Hill
AU - Sudeep Shivakumar
AU - Vicky Tagalakis
AU - Phil Wells
AU - Marc Carrier
PY - 2026
DA - 2026/10/25
JO - Cancer Medicine
DO - 10.1002/cam4.72423
UR - https://doi.org/10.1002/cam4.72423
AB - Background: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. The AVERT trial showed apixaban thromboprophylaxis reduced VTE in intermediate‐to‐high‐risk patients initiating chemotherapy. However, the efficacy and safety of apixaban according to baseline chemotherapy class remain incompletely characterized. Methods: We conducted a post hoc analysis stratified by chemotherapy class of the randomized, double‐blind, placebo‐controlled AVERT trial comparing apixaban (2.5 mg twice daily) with placebo in ambulatory cancer patients initiating chemotherapy. The primary efficacy outcome was VTE, and the primary safety outcome was clinically relevant bleeding (major or clinically relevant non major bleeding (CRNMB)) per ISTH criteria. A subgroup analysis compared platinum‐based with non‐platinum chemotherapy. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CI), adjusted for age, sex, and study site. Treatment‐by‐platinum interaction terms were used to assess effect modification by platinum exposure. Results: A total of 563 patients were included and categorized by one or more chemotherapy classes at randomization. Compared with placebo, apixaban appeared to reduce VTE in patients on platinum (HR 0.30, 95% CI 0.16–0.57), taxane (HR 0.42, 95% CI 0.23–0.75), taxane‐platinum (HR 0.28, 95% CI 0.12–0.68), topoisomerase inhibitor (HR 0.32, 95% CI 0.19–0.53), and antimetabolite regimens (HR 0.25, 95% CI 0.12–0.54), without increased bleeding. Among placebo‐treated patients, platinum‐based chemotherapy was associated with a higher risk of VTE compared with non‐platinum regimens (HR 2.25, 95% CI 1.48–3.42), whereas no statistically significant difference was observed among apixaban‐treated patients. Treatment‐by‐platinum interaction testing did not demonstrate significant effect modification by platinum exposure. Conclusion: In this exploratory, hypothesis‐generating analysis, apixaban thromboprophylaxis was associated with reduced VTE across several chemotherapy regimens with generally acceptable safety outcomes. Patients receiving platinum‐based chemotherapy may derive greater absolute benefit from thromboprophylaxis in the setting of higher underlying thrombotic risk.
SN - 2045-7634
ER -