Venous Thromboembolism Reporting in Fusion-Positive NSCLC Treated with Tyrosine Kinase Inhibitors: A Systematic Review of Safety Reporting and Protocol-Level Provisions in Phase I-IV Clinical Trials.

Abstract

Venous thromboembolism (VTE) is increasingly recognized as a clinically relevant complication in patients with fusion-positive non-small cell lung cancer (NSCLC). However, the completeness and consistency of thromboembolic safety reporting in clinical trials of tyrosine kinase inhibitors remain poorly characterized. We performed a systematic review of phase I-IV clinical trials evaluating targeted therapies in fusion-positive NSCLC. Protocols, publications, and online trial registry updates were systematically reviewed to assess thromboembolic event ascertainment, reporting practices, protocol-level anticoagulant therapy provisions, and VTE-related eligibility criteria. A total of 108 reporting sources from 61 study entries (58 unique trials) were reviewed. Pulmonary embolism and deep vein thrombosis were the predominant reported events. VTE-related information was highly fragmented across reporting sources: 14 study entries reported events exclusively through full-text publications, 19 exclusively through online trial updates, and 15 through both sources. Study protocols rarely prespecified thromboembolic events as dedicated safety outcomes, more commonly addressing them in eligibility criteria, anticoagulant therapy provisions, or differential diagnosis guidance. More than 40% of study entries lacked protocol-level anticoagulant therapy provisions and nearly 60% lacked VTE-related eligibility restrictions. Marked heterogeneity was observed in event definitions, reporting practices, safety ascertainment, and observation periods. In fusion-positive NSCLC trials, heterogeneity in event ascertainment and reporting, rather than a true scarcity of thromboembolic events, represents a major limitation of the available evidence. Greater standardization of safety reporting and integration of trial registry and publication data may improve the completeness, comparability, and interpretability of future studies.