Primary Thromboprophylaxis in Ambulatory Pancreatic Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Patients with pancreatic cancer (PC) carry the highest risk of venous thromboembolism (VTE) amongst all cancer patients. Appropriate use of primary thromboprophylaxis might significantly and safely reduce its burden. We performed a systematic review of published studies and meeting abstracts using MEDLINE and EMBASE through July 2020 to evaluate the efficacy and safety of primary thromboprophylaxis in ambulatory PC patients receiving chemotherapy. The Mantel–Haenszel random effect model was used to estimate the pooled event-based risk ratio (RR) and the pooled absolute risk difference (RD) with a 95% confidence interval (CI). Five randomized controlled studies with 1003 PC patients were included in this meta-analysis. Compared to placebo, thromboprophylaxis significantly decreased the risk of VTE (pooled RR 0.31, 95% CI 0.19–0.51, p < 0.00001, I2 = 8%; absolute RD −0.08, 95% CI −0.12–−0.05, p < 0.00001, I2 = 0%), with an estimated number needed to treat of 11.9 patients to prevent one VTE event. Similar reductions of VTE were observed in studies with parenteral (RR 0.30, 95% CI 0.17–0.53) versus oral anticoagulants (RR 0.37, 95% CI 0.14–0.99) and in studies using prophylactic doses of anticoagulants (RR 0.34, 95% CI 0.17–0.70) versus supra-prophylactic doses of anticoagulants (RR 0.27, 95% CI 0.08–0.90). The pooled RR for major bleeding was 1.08 (95% CI 0.47–2.52, p = 0.85, I2 = 0%) and the absolute RD was 0.00 (95% CI −0.02–0.03, p = 0.85, I2 = 0%). Evidence supports a net clinical benefit of thromboprophylaxis in ambulatory PC patients receiving chemotherapy. Adequately powered randomized phase III studies assessing the most effective anticoagulant and the optimal dose, schedule and duration of thromboprophylaxis to be used are warranted.

The Clinical Applicability of Primary Thromboprophylaxis in Ambulatory Patients With Pancreatic Cancer

“…Another meta-analysis including a heterogeneous group of ambulatory cancer patients treated with LMWH showed a reduction in VTE incidence by 49% (95% CI, 0.43-0.56) with no significant increase in MB. 25 This study also reported a significant VTE reduction with thromboprophylaxis in PDAC-specific patient population (odds ratio, 0.26; 95% CI, 0.14-0.48) similar to the results from Tun et al 25 An updated meta-analysis of PATP in ambulatory patients with PDAC by Frere et al, 26 also demonstrated that PATP significantly reduced the risk of VTE (pooled RR, 0.31 [95% CI, 0.19-0.51; P < 0.00001, I 2 = 8%]; absolute risk difference, −0.08 [95% CI, −0.12 to −0.05; P < 0.00001, I 2 = 0%]), with an estimated NNT of 11.9 patients to prevent one VTE event.…”

Incidence, timing and risk factors of venous thromboembolic events in patients with pancreatic cancer

“…They conclude that there is evidence that thromboprophylaxis could provide clinical benefit for patients during chemotherapy, but additional trials are necessary to determine the exact type of anticoagulant as well as dosage, duration etc. [36] This conclusion is supported by the review of Mulder et al discussing international guidelines for thromboprophylaxis in cancer patients. [37] However, in the current study, most VTEs (51 out of 64, 80%) occurred in the advanced phase of disease in which patients no longer received any medical treatment.…”

Early detection of venous thromboembolism after the initiation of chemotherapy predicts a poor prognosis in patients with unresectable metastatic pancreatic cancer who underwent first-line chemotherapy with gemcitabine plus nab-paclitaxel

“…By contrast, VTE has a high recurrence rate, and anticoagulation is associated with bleeding events, including gastrointestinal bleeding [ 14 , 25 ]. Recently, a meta-analysis of 1003 pancreatic cancer patients has revealed that anticoagulation therapy significantly reduced the risk of symptomatic VTE without increasing major bleeding [ 26 ]. Considering these results, the International Initiative on Thrombosis and Cancer (14) and American Society of Clinical Oncology Clinical Practice [ 25 ] guidelines recommend anticoagulation therapy with apixaban or rivaroxaban in cancer outpatients undergoing chemotherapy with a Khorana score ≥ 2, no bleeding risk and no drug-drug interactions (Grade 1B) [ 14 ].…”