Impact of Primary Ambulatory Thromboprophylaxis (PATP) with Low-Molecular Weight Heparins (LMWHs) on Survival in Patients with Locally Advanced or Metastatic Lung Cancer (LC) Receiving Chemotherapy

Abstract

Introduction: LC is the leading cause of cancer mortality in USA. PATP was provided in experimental trials to decrease the venous thromboembolism (VTE) rates and to provide anti-tumor effect with ultimate aim to improve survival in patients with solid cancers as VTE is the second leading cause of death in cancer patients. We undertook a systematic review and meta- analysis of randomized controlled trials (RCTs) to determine the impact of PATP with LMWHs on overall survival (OS) in patients with locally advanced or metastatic LC. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through July 26, 2019. The references of all potential studies were also reviewed for any additional relevant studies. RCTs utilizing PATP with LMWHs in patients with locally advanced or metastatic lung cancer were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for progression or metastasis free survival and OS with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q -statistic. Random effects model was applied. Results: A total of 3,452 patients with lung cancer from six RCTs were included in our meta-analysis. The prophylactic doses of bemiparin, dalteparin, tinzaparin, nadroparin and intermediate dose of enoxaparin were used in the studies. The duration of LMWH ranged from 3 to 6 months. The randomization ratio was 1 to 1 in all studies. The I2statistic for heterogeneity was 64, suggesting moderate heterogeneity among RCTs. The pooled HR for OS was not statistically significant at 1.02 (95% CI: 0.83-1.26; P = 0.83). In a subset of small cell lung cancer (SCLC) patients, the pooled HR for OS was 1.03 (95% CI: 0.72-1.48; P = 0.85). The HR for OS was noted at 1.70 (95% CI: 0.70-4.15; P = 0.24) in patients with limited stage SCLC. In a subset of non-small cell lung cancer, the pooled HR of OS was 1.00 (95% CI: 0.79-1.26; P = 0.98). The pooled HR for progression or metastasis free survivalwas 1.03 (95% CI: 0.86-1.24; P = 0.74) according to an analysis of 5 RCTs. Conclusions: Our meta- analysis demonstrated that no survival advantage was noted with the addition of PATP with LMWHs to routine standard chemotherapy in patients with locally advanced or metastatic LC, regardless of histology types as well as stages of SCLC. Disclosures Oo: Medical Education Speakers Network: Honoraria; Janssen and Janssen: Other: Research: site co-investigator .