Patterns of Thromboembolism in Patients with Advanced Pancreatic Cancer Undergoing First-Line Chemotherapy with FOLFIRINOX or Gemcitabine/nab-Paclitaxel

Abstract

Introduction: Recent advances in prophylactic anticoagulation and antineoplastic treatment for aPC warrant an updated reassessment of thromboembolic risk in this population. This multicenter retrospective cohort study aims to comprehensively characterize incidence, risk factors and outcomes of venous (VTE) and arterial thromboembolism (ATE) in homogenously treated patients with aPC. Methods: Four-hundred-fifty-five patients with aPC undergoing palliative 1st-line chemotherapy (Gemcitabine/nab-Paclitaxel (GN) or FOLIRINOX) were included. Primary outcomes were objectively confirmed VTE and/or ATE. Results: Over a median follow-up of 26 months, 86 VTE (cumulative incidence: 20.0% [95% confidence interval (CI): 16.3-24.0]) and 11 ATE events (cumulative incidence: 2.8% [95%CI: 1.5-4.9]) were observed. VTE diagnosis was associated with increased mortality (transition hazard ratio (THR): 1.59 [95%CI 1.21-2.09]) and increased risk of disease progression (THR: 1.47 [95%CI: 1.08-2.01]), while the impact of ATE on mortality was numerically but not statistically significant (THR: 1.85 [95%CI: 0.87-3.94]). The strongest predictor of increased VTE risk was history of cancer-associated VTE (subdistribution hazard ratio (SHR) 3.29 [95%CI: 2.09-5.18]), while the Khorana-score (SHR 0.78 [0.57-1.06]) failed to predict VTE risk. A history of cerebrovascular disease was associated with markedly increased ATE risk (SHR: 22.05 [95%CI: 6.83-71.22], p<0.001), especially ischemic stroke. Risk of VTE/ATE did not significantly differ according to type of 1st line chemotherapy. Conclusion: Patients with aPC undergoing palliative 1st-line chemotherapy with FOLFIRINOX or GN face a high risk for VTE/ATE and its diagnosis is linked to worse clinical outcomes. VTE-risk prediction models have limited ability to sub-stratify thrombotic events in this high-risk scenario.

Unanswered questions in cancer‐associated thrombosis

“…In a multicentre, retrospective cohort study of 455 patients with advanced or metastatic pancreatic cancer, 25 of 57 patients who had cancer-associated VTE developed recurrent VTE after initiation of first-line chemotherapy. 60 The cumulative incidence of recurrent VTE over a median 26-month follow-up was highest in this group at 46.7%, compared with 15.5% in those who had no prior history of VTE.…”

“…Importantly, a higher proportion of patients receiving anticoagulation beyond six months had advanced disease stage and received ongoing systemic cancer therapy compared to those who stopped anticoagulation, suggesting that underlying differences in patient and cancer characteristics contributed to the decision to continue or stop anticoagulation as well as the observed differences in VTE recurrence rates. In a multicentre, retrospective cohort study of 455 patients with advanced or metastatic pancreatic cancer, 25 of 57 patients who had cancer‐associated VTE developed recurrent VTE after initiation of first‐line chemotherapy 60 . The cumulative incidence of recurrent VTE over a median 26‐month follow‐up was highest in this group at 46.7%, compared with 15.5% in those who had no prior history of VTE.…”

Thrombosis and Haemostasis 2022 Editors' Choice Papers

“…40 In patients with advanced pancreatic cancer, who experienced palliative first-line chemotherapy, history of cancerrelated VTE emerged as the strongest risk factor. 41 The negative outcome of these patients for developing VTE increased with cancer progression and led to higher mortality rate. In addition, known prothrombotic risk factors and both Khorana and CONKO scores failed to predict for VTE risk in the patient cohort, indicating that these prediction models could not be applied for this cancer-specific setting.…”

Hemostasis and cancer: Impact of haemostatic biomarkers for the prediction of clinical outcomes in patients with cancer

“… 7 Further, VTE diagnosis is an independent predictor for decreased survival in cancer patients, suggesting overt thrombotic manifestations in patients with cancer as a reflection of more aggressive underlying cancer phenotypes, disease progression, and treatment failure. 8 , 9 , 10 , 11 …”

“…7 Further, VTE diagnosis is an independent predictor for decreased survival in cancer patients, suggesting overt thrombotic manifestations in patients with cancer as a reflection of more aggressive underlying cancer phenotypes, disease progression, and treatment failure. [8][9][10][11] Different pathophysiological pathways were identified in the interplay between cancer and different components of the hemostatic system. The overexpression of procoagulant molecules, most prominently tissue factor (TF) as the main activator of coagulation in vivo, was found in different cancers.…”