Updated Meta-Analysis of Randomized Controlled Trials on Primary Outpatient Thromboprophylaxis (POTP) in Patients with Lung Cancer Receiving Chemotherapy

Introduction Lung cancer (LC) is the leading cause of cancer mortality in the USA. Thrombosis is the second leading cause of death in cancer patients and in recent years, several studies have been conducted to determine beneficial effect of POTP in reduction of VTE (venous thromboembolism) rate in solid cancer patients with the aim to improve the overall survival. We performed an updated meta- analysis of randomized control trials (RCTs) to determine the benefit and risk of POTP with low-molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) in patients with LC receiving chemotherapy. Methods We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2023. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Fixed effects model was applied. Results A total of 5,434 patients with LC from five RCTs and subgroups of another five RCTs were included in our meta-analysis. The prophylactic doses of bemiparin, certoparin, dalteparin, nadroparin, semuloparin and tinzaparin, intermediate dose of enoxaparin and prophylactic dose of rivaroxaban and apixaban were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I 2 statistic for heterogeneity was 0, suggesting homogeneity among RCTs. The VTE incidence was 114 (4.12%) in PATP group and 207 (7.8%) in control group with a RR of 0.53 (95% CI: 0.43 to 0.67, P < 0.00001). The absolute RD in VTE was -0.04 (95% CI: -0.05 to -0.02, P < 0.00001) with an estimate of the number needed to treat (NNT) of 25 to prevent one VTE event. In subgroup analysis of PATP trials treated with LMWHs in study arm, VTE events were reported in 112 (4.2%) in PATP group and 202 (7.9%) in control group with a RR of 0.54 (95% CI: 0.43 to 0.67, P < 0.00001). The absolute RD in VTE was -0.04 (95% CI: -0.05 to -0.02, P < 0.00001). In subgroup analysis of PATP trials treated with DOACs in study arm, VTE events were reported in 2 (2.2%) in PATP group and 5 (5%) in control group with a RR of 0.46