Association of Venous Thromboembolism and Early Mortality in Patients with Newly Diagnosed Metastatic Non-Small Cell Lung Cancer

Abstract

Purpose

To explore the relationship between venous thromboembolism (VTE) and early mortality (within six months) in Chinese patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) after entering the era of precision treatment.

Methods

A cohort of 706 consecutive subjects with newly diagnosed metastatic NSCLC were prospectively observed. Clinical and survival data were recorded over a six-month follow-up period. The predictive factors for the occurrence of VTE and the relationship with early mortality were evaluated through univariate and multivariate analyses.

Results

During the six-month follow-up period, VTE events occurred in 12.2% (86/706) of the enrolled patients. In the multivariate analyses for VTE, an age older than 70 years (vs < 70: sub-distribution hazard radio [SHR], 1.678; 95% confidence interval (CI), 1.073–2.600; P=0.022), an Eastern Cooperative Oncology Group performance status ≥2 (vs 0/1: SHR, 1.946; 95% CI, 1.277–2.970; P=0.002), and having an ALK rearrangement (vs non-rearrangement: SHR, 2.377; 95% CI, 1.186–4.760; P=0.015) were significantly associated with the occurrence of VTE. Within six months, 116 subjects (16.4%) died, and the occurrence of VTE (vs no VTE: adjusted HR: 1.863; 95% CI: 1.178–2.947, P=0.008) was remarkably associated with early mortality. Further analysis showed 98 patients (13.9%) with early mortality had EGFR/ALK wild-type genes, with a risk of early mortality 5.935-fold higher than that of patients with an EGFR mutation/ALK rearrangement. Finally, subgroup analyses showed that VTE occurrence was a significant factor for predicting early mortality in patients with EGFR/ALK wild-type genes (adjusted HR: 1.682; 95% CI: 1.023–2.768, P=0.041).

Conclusion

Patients with an EGFR mutation/ALK rearrangement had a significantly decreased risk of early mortality in the era of targeted therapy; however, VTE occurrence remained an important predictor for early mortality in metastatic NSCLC patients, especially in patients with EGFR/ALK wild-type genes.

Keywords:

• venous thromboembolism
• non-small cell lung cancer
• early mortality

Acknowledgments

The authors greatly appreciate all patients who contributed to this study and thank Yuanhua Yang (MD, PhD), Zhanhong Ma (MD), and Lei Zhang (MD) as the members of the review panel who evaluated the VTE events in this study.

Abbreviations

VTE, venous thromboembolism; NSCLC, non-small cell lung cancer; DVT, deep venous thromboembolism; PE, pulmonary embolism; BMI, body mass index; EGFR, epidermal growth factor receptor; KRAS, Kirsten rat sarcoma; ALK, anaplastic lymphoma kinase; Cl, Confidence interval; ECOG, Eastern Cooperative Oncology Group; PS, performance status; SHR, sub-distribution hazard radio; HR, hazard ratio; TKI, tyrosine kinase inhibitor.

Data Sharing Statement

All data analyzed during the current study are available from the corresponding author.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors have no conflicts of interest to declare.