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. 2021 Mar;10(3):1512-1524.
doi: 10.21037/tlcr-20-1290.

High discrepancy in thrombotic events in non-small cell lung cancer patients with different genomic alterations

Yiwei Liu  1 , Wanying Wang  1 , Fengying Wu  1 , Guanghui Gao  1 , Jian Xu  1 , Xuefei Li  2 , Chao Zhao  2 , Shuo Yang  1 , Shiqi Mao  1 , Yingying Pan  1 , Keyi Jia  1 , Chuchu Shao  1 , Bin Chen  1 , Shengxiang Ren  1 , Caicun Zhou  1
Affiliations

High discrepancy in thrombotic events in non-small cell lung cancer patients with different genomic alterations

Yiwei Liu et al. Transl Lung Cancer Res. 2021 Mar.

Abstract

Background: Acute complications, such as venous thromboembolism (VTE), are common in patients with advanced severe lung cancers. However, current VTE risk scores cannot adequately identify high-risk patients with non-small cell lung cancer (NSCLC). The study proposed to elucidated the incidence of thromboembolism (TE) in patients with different oncogenic aberrations and the impact of these aberrations on the efficacy of targeted therapy in patients with NSCLC.

Methods: A systemic review was conducted in Web of Science, PubMed, Embase and the Cochrane Library to evaluate the incidence of TE in different molecular subtypes of NSCLC. Data from patients diagnosed of advanced NSCLC who harboring anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) rearrangements since 2016 to 2019 were also retrospectively collected. A meta-analysis with random-effects model, sensitivity analysis and publication bias were performed. The principal summary measure was incidence of thrombotic events in NSCLC patients. And the efficacy of tyrosine kinase inhibitor (TKI) therapy was compared between the two subgroups.

Results: A total of 5,767 cases from 20 studies were included in the analysis of the incidence of thrombosis in patients with different oncogenic alterations. The pooled analysis showed a higher risk of thrombosis in ROS1-fusion types (41%, 95% CI: 35-47%) and ALK-fusion types (30%, 95% CI: 24-37%) than in EGFR-mutation (12%, 95% CI: 8-17%), KRAS-mutation (25%, 95% CI: 13-50%), and wild-type (14%, 95% CI: 10-20%) cases. A high prevalence of thrombosis (ALK: 24.4%; ROS1: 32.6%) was observed in the Shanghai Pulmonary Hospital (SPH) cohort of 224 patients with ALK or ROS1 fusion. Furthermore, patients with embolism had significantly shorter progression-free survival (PFS) after TKI therapy than those without embolism, both in the ALK+ cohort (5.6 vs. 12.9 months, P<0.0001) and in the ROS1+ cohort (9.6 vs. 17.6 months, P=0.0481).

Conclusions: NSCLC patients with ALK/ROS1 rearrangements are more likely to develop thrombosis than patients with other oncogenic alterations. Thrombosis may also be associated with an inferior response and PFS after TKI therapy.

Keywords: Non-small cell lung cancer (NSCLC); ROS1; anaplastic lymphoma kinase (ALK); thromboembolism (TE).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-1290). CZ has served as an unpaid editorial board member of Translational Lung Cancer Research from Aug 2020 to Jul 2022. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Flowchart of the identification of eligible studies for the meta-analysis.
Figure 2
Figure 2
Meta-analysis (forest plot) of the prevalence of thrombotic events in lung cancer patients.
Figure 3
Figure 3
Subgroup analyses of the prevalence of thrombosis based on patient’s mutation status. (A) ALK-fusion; (B) ROS1-fusion; (C) KRAS-mutant; (D) EGFR-mutant; (E) wild-type. ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; KRAS, Kirsten rat sarcoma viral oncogene homolog; ROS1, ROS pro-oncogene 1 receptor tyrosine kinase.
Figure 4
Figure 4
Flowchart showing the selection of eligible patients.
Figure 5
Figure 5
Comparison of TKI response and PFS between the VTE group and non-VTE group in the ALK-fusion and ROS1-fusion cohort, respectively. (A) Response to TKI therapy among ALK+ patients; (B) PFS of ALK+ patients treated with TKI therapy; (C) response to TKI therapy among ROS1+ patients; (D) PFS of ROS1+ patients treated with TKI therapy. ALK, anaplastic lymphoma kinase; PFS, progression-free survival; ROS1, ROS pro-oncogene 1 receptor tyrosine kinase; TKI, tyrosine kinase inhibitor; VTE, venous thromboembolis.
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