Advanced pancreatic cancer is associated with a significantly increased risk of venous thromboembolism: within one year, approximately one fifth of patients suffer such a complication – with devastating consequences. What is the best way to protect this population? There are several studies on this. For example, the CONKO-004 study, which was finally published in May 2015 after a long wait, demonstrates the preventive efficacy of low-molecular-weight heparin (Enoxaparin®).
It has been adequately demonstrated that enoxaparin can prevent venous thromboembolism (VTE). Some smaller studies had also already shown a benefit in cancer patients. The authors of the CONKO-004 study from the Charité in Berlin were primarily interested in investigating the situation in outpatients with pancreatic cancer. For this purpose, they randomized a total of 312 individuals with histologically confirmed advanced pancreatic cancer into two groups: One with first-line outpatient chemotherapy and enoxaparin prophylaxis (daily 1 mg/kg bw) and one with chemotherapy alone (control arm). Chemotherapy consisted of gemcitabine, fluorouracil, folinic acid, and cisplatin in patients in good condition and with low creatinine, and only gemcitabine in those in poor condition and with elevated creatinine. After three months, all patients received gemcitabine and those in the study group received daily fixed 40 mg enoxaparin.
The results had been presented at a previous ASCO meeting and later supplemented with survival data. Meanwhile, after a long wait, they have appeared in the Journal of Clinical Oncology. The aim of the study was to determine the extent to which enoxaparin reduces the rate of VTE and whether there is also an effect on progression-free or overall survival.
Risk significantly reduced by prophylaxis
Among the 152 patients in the control group, 15 symptomatic VTE occurred within the first three months, compared with only two among the 160 subjects in the enoxaparin arm. Thus, the risk of VTE was significantly reduced by 88% with enoxaparin prophylaxis. Overall, after approximately one year, the cumulative incidence of symptomatic VTE was finally 15.1% (control) vs. 6.4% (enoxaparin, HR 0.40; 95% CI 0.19-0.83; p=0.01).
And what about the risk for severe bleeding? In fact, such cases were more frequent in the enoxaparin group, although not significantly: compared to the five major bleeding events in the control group, seven such complications occurred under heparin (HR 1.4; 95% CI 0.35-3.72; p=1.0).
No effect was seen in survival: Neither progression-free (HR1.06) nor overall survival (HR 1.01) differences reached significance.
The authors conclude that primary VTE prevention in outpatients with advanced pancreatic cancer is effective and well feasible. Administration of enoxaparin did not affect the efficacy of tumor treatment.
Open questions
Despite the final publication of the CONKO-004 results, important questions remain:
- Which patients with advanced pancreatic cancer are eligible for VTE prophylaxis or how should the risk for VTE and the risk for bleeding be weighted in patient selection?
- Which anticoagulant, dose, and therapeutic regimen is best to use in outpatients?
Because of the large variability with respect to individual risk, the limited number of large and good randomized-controlled trials, and the risk of bleeding complications, guidelines, e.g., those of ASCO, currently do not recommend routine thromboprophylaxis in outpatients, including those with advanced pancreatic cancer.
Source: Pelzer U, et al: Efficacy of Prophylactic Low-Molecular Weight Heparin for Ambulatory Patients With Advanced Pancreatic Cancer: Outcomes From the CONKO-004 Trial. J Clin Oncol 2015; doi: 10.1200/JCO.2014.55.1481 (Epub ahead of print).
InFo ONCOLOGY & HEMATOLOGY 2015; 3(7): 4-5.
