Thromboprophylaxis in Portuguese Cancer Outpatients: Real-World Insights and Patient Characterization

Venous thromboembolism (VTE) affects up to 20% of cancer patients, presenting a four-to-seven-fold increased risk compared to the general population [1,2]. This elevated risk is attributed to patient-related factors, the tumor, and antineoplastic treatments [3]. When deciding on thromboprophylaxis, these factors, along with the potential for bleeding, costs, and the impact on the patient’s quality of life, are taken into consideration [4,5]. Low-molecular-weight heparin (LMWH) and Direct Oral Anticoagulants (DOAC) are commonly prescribed to cancer outpatients, though potential drug interactions and bleeding risks must be managed carefully [6,7].

Over the years, various risk assessment models (RAMs) for cancer-associated thrombosis (CAT) have been developed to aid in selecting cancer outpatients for primary thromboprophylaxis and improving risk stratification and outcomes [8,9]. Despite these advancements, controversies remain regarding the optimal use of primary thromboprophylaxis [10]. Better characterization of patients at increased risk of CAT and bleeding events under primary thromboprophylaxis is crucial for identifying those with a favourable benefit-to-risk ratio, especially since existing evidence primarily comes from clinical trials often involving a selected patient population [8].

In the specific context of Portuguese cancer outpatients, Dr. Joana Liz Pimenta conducted a real-world evidence (RWE) multicentric cross-sectional study to understand how to manage and ensure the safety and effectiveness of thromboprophylaxis in this population. Additionally, the study explored the relationship between CAT and bleeding events during thromboprophylaxis using accessible markers and RAMs in clinical settings. The identification of predictive biomarkers could lead to the development of a new RAM for more personalized and precise interventions [10].

Study Design and Methodology: Patient Cohort, Data Collection, and Endpoint Analysis

The study cohort consisted of 124 adult patients with histologically confirmed solid tumors receiving primary thromboprophylaxis in an ambulatory setting across eight Oncology Departments in Portugal. Patients self-administed the thromboprophylaxis medication, which was selected by their oncologist, including its duration. At the onset of systemic treatment, data were collected by reviewing hospital electronic medical records, encompassing patient follow-up, demographic details, clinicopathological factors, and information on systemic and local antineoplastic treatments [10].

The study’s primary endpoint focused on CAT, encompassing both confirmed VTE and arterial thromboembolism (ATE), involving a detailed analysis of the thrombosis location, diagnostic conditions, and dates of occurrence. Secondary endpoints were also considered, including the occurrence of bleeding events, categorized as either minor or major, cancer progression and mortality [10].

Descriptive statistics were employed to address each objective, with subgroup analyses considering distinct patient and treatment groups. To uncover risk factors for various events, variables including patient’s age, sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), body mass index (BMI), primary tumor location, vascular/lymphatic compression, history of VTE, D-dimer levels, blood count, and antineoplastic treatments involving platinum and/or gemcitabine were assessed. These variables also served as the basis for calculating several RAMs: the Khorana score (KS), Onkotev model, Protects score, and Conko-004 score [10].

Tailoring Thromboprophylaxis: Lessons from the Portuguese Cancer Patient Study

The group of participants consisted primarily of elderly individuals with comorbidities, balanced in gender, maintaining good PS and healthy BMI, predominantly suffering from high thrombogenic tumors such as pancreatic, gastric, and lung cancers, often in advanced stages [10].

Likely due to KS being the most frequently used RAM for deciding thromboprophylaxis, in the study population it had the highest number of patients in the higher risk categories. However, consistent with previous studies, the Onkotev score proved superior to KS in guiding individualized thromboprophylaxis for VTE in this population, highlighting the importance of a case-by-case evaluation [10-11].

In addition, a statistically significant association has been reported between known risk factors, such as elevated D-dimer levels, vascular compression, and previous VTE, and the occurrence of CAT, showing the relationship between tumor aggressiveness and thrombo-inflammation. Taken together, these results represent a matter of discussion for healthcare professionals, as they highlighted a very high risk subgroup that suffers from CAT even under thromboprophylaxis that probably would benefit from more tailored prophylaxis strategies [10].

Regarding primary thromboprophylaxis, in line with guidelines for tumors with a higher risk of bleeding, LMWHs were identified as the preferred class. Interestingly, regarding drug choices both tinzaparin (an LMWH) and rivaroxaban (a DOAC) were used equally, with no significant differences reported in CAT or bleeding event rates nor in the duration of thromboprophylaxis (median period of 5.4 months) between the two anticoagulants. This highlights effective drug-patient decision-making and indicates a trend toward individualized thromboprophylaxis choices [9-10].

Overall, thromboprophylaxis proved to be effective and safe, with 81% of patients experiencing no adverse events. Regarding CAT events, they occurred in 11%, were mainly VTE and symptomatic. Interestingly ATE and VTE at unusual sites were higher than anticipated, at 3%. The significance of maintaining thromboprophylaxis for at least six months with continuous monitoring until completion is highlighted by the observation that CAT events occurred around the 6^th month of thromboprophylaxis. Regarding bleeding events, they only occurred in 9%, majority classified as minor, and not significantly linked to patient deaths [10].

Finally, further studies with larger samples are needed to confirm the results of the present study. This would help establish new RAMs for patient selection based on population groups and improve knowledge about the optimal drug duration and dosage, as well as the assessment of patients’ perspectives and quality of life concerning thromboprophylaxis. Additionally, evaluating international adherence to guidelines, identifying potential challenges to implementing CAT prevention, and discovering more predictive factors for VTE and bleeding would enable the development of more effective thromboprophylaxis strategies and consequently improving cancer patients life’s [10].

Conclusions

The findings of this study, representing the first Portuguese RWE of primary thromboprophylaxis in cancer outpatients, support its use in medium-to-high-risk cancer patients, since large majority of patients did not experience any VTE nor bleeding events. Additionally, the study reveals a very high-risk population, that experience CAT under thromboprophylaxis, with predictive factors easily assessed in clinical practice for them, such as vascular compression, previous VTE, elevated D-dimer levels and cancer progression. This study highlights the need and contributes for a more tailored strategies to improve outcomes.

References

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