Efficacy and safety of vascular endothelial growth factor receptor tyrosine kinase inhibitors in the treatment of advanced thyroid cancer: a meta-analysis of randomized controlled trials

Yimaer, Wufuer; Abudouyimu, Aizizi; Tian, Ye; Magaoweiya, Sailike; Bagedati, Duman; Wen, Hao

doi:10.2147/ott.s102265

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…Recently, different kinds of novel TKIs have been investigated in cancer patients and shown improving overall survival and progression-free survival. Indeed, two previously published meta-analyses had demonstrated that TKIs treatment in advanced/metastatic thyroid cancer patients was associated with a significantly improved overall survival and progression-free survival, and higher incidence of diarrhea, rash, and hypertension was observed in TKIs treatment group [41, 42]. But the overall incidence and risk of severe ATEs/VTEs associated with TKIs in TCs patients remains undetermined, although these toxicities have been observed in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Risk of venous and arterial thromboembolic events associated with tyrosine kinase inhibitors in advanced thyroid cancer: a meta-analysis and systematic review

Bai

Li²,

et al. 2018

Oncotarget

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Aims: To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs) associated with tyrosine kinase inhibitors (TKIs) in advanced thyroid cancer patients. Materials and Methods: We comprehensively searched EMBASE, Pubmed, and Cochrane Library for relevant trials. Prospective clinical trials evaluating the role of TKIs alone in advanced thyroid cancer patients were included for analysis. Data on high-grade VTEs and ATEs were extracted. The pooled incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were pooled according to the heterogeneity of included trials. Results: A total of 1,781 patients from 12 trials, including four randomized controlled trials and eight phase II single arm trials, were included for analysis. Our results showed that the overall incidence of high-grade ATEs and VTEs associated with TKIs were 1.4% and 3.3%, and TKIs treatment in advanced TCs patients significantly increased the risk of developing high-grade ATEs (Peto OR 4.72, 95% CI: 1.18–18.95, p = 0.029), but not for high-grade VTEs (Peto OR 1.36, 95% CI: 0.51–3.64, p = 0.54) when compared to placebo. The most common specific causes of ATEs were myocardial infarction (28.6%) and ischemic cerebrovascular events (21.4%), respectively. Conclusions: TKIs treatment in advanced thyroid cancer significantly increases the risk of developing high-grade ATEs but not for VTEs. Clinicians should be cautious about the risk of severe ATEs associated with TKIs to maximize the benefits and minimize the toxicities.

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Section: Discussionmentioning

confidence: 99%

Risk of venous and arterial thromboembolic events associated with tyrosine kinase inhibitors in advanced thyroid cancer: a meta-analysis and systematic review

Bai

Li²,

et al. 2018

Oncotarget

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Lenvatinib and sorafenib for differentiated thyroid cancer after radioactive iodine: a systematic review and economic evaluation

Fleeman

Houten

Bagust

et al. 2020

Health Technol Assess

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Background Thyroid cancer is a rare cancer, accounting for only 1% of all malignancies in England and Wales. Differentiated thyroid cancer (DTC) accounts for ≈94% of all thyroid cancers. Patients with DTC often require treatment with radioactive iodine. Treatment for DTC that is refractory to radioactive iodine [radioactive iodine-refractory DTC (RR-DTC)] is often limited to best supportive care (BSC). Objectives We aimed to assess the clinical effectiveness and cost-effectiveness of lenvatinib (Lenvima®; Eisai Ltd, Hertfordshire, UK) and sorafenib (Nexar®; Bayer HealthCare, Leverkusen, Germany) for the treatment of patients with RR-DTC. Data sources EMBASE, MEDLINE, PubMed, The Cochrane Library and EconLit were searched (date range 1999 to 10 January 2017; searched on 10 January 2017). The bibliographies of retrieved citations were also examined. Review methods We searched for randomised controlled trials (RCTs), systematic reviews, prospective observational studies and economic evaluations of lenvatinib or sorafenib. In the absence of relevant economic evaluations, we constructed a de novo economic model to compare the cost-effectiveness of lenvatinib and sorafenib with that of BSC. Results Two RCTs were identified: SELECT (Study of [E7080] LEnvatinib in 131I-refractory differentiated Cancer of the Thyroid) and DECISION (StuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine-refractory thyrOid caNcer). Lenvatinib and sorafenib were both reported to improve median progression-free survival (PFS) compared with placebo: 18.3 months (lenvatinib) vs. 3.6 months (placebo) and 10.8 months (sorafenib) vs. 5.8 months (placebo). Patient crossover was high (≥ 75%) in both trials, confounding estimates of overall survival (OS). Using OS data adjusted for crossover, trial authors reported a statistically significant improvement in OS for patients treated with lenvatinib compared with those given placebo (SELECT) but not for patients treated with sorafenib compared with those given placebo (DECISION). Both lenvatinib and sorafenib increased the incidence of adverse events (AEs), and dose reductions were required (for > 60% of patients). The results from nine prospective observational studies and 13 systematic reviews of lenvatinib or sorafenib were broadly comparable to those from the RCTs. Health-related quality-of-life (HRQoL) data were collected only in DECISION. We considered the feasibility of comparing lenvatinib with sorafenib via an indirect comparison but concluded that this would not be appropriate because of differences in trial and participant characteristics, risk profiles of the participants in the placebo arms and because the proportional hazard assumption was violated for five of the six survival outcomes available from the trials. In the base-case economic analysis, using list prices only, the cost-effectiveness comparison of lenvatinib versus BSC yields an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of £65,872, and the comparison of sorafenib versus BSC yields an ICER of £85,644 per QALY gained. The deterministic sensitivity analyses show that none of the variations lowered the base-case ICERs to < £50,000 per QALY gained. Limitations We consider that it is not possible to compare the clinical effectiveness or cost-effectiveness of lenvatinib and sorafenib. Conclusions Compared with placebo/BSC, treatment with lenvatinib or sorafenib results in an improvement in PFS, objective tumour response rate and possibly OS, but dose modifications were required to treat AEs. Both treatments exhibit estimated ICERs of > £50,000 per QALY gained. Further research should include examination of the effects of lenvatinib, sorafenib and BSC (including HRQoL) for both symptomatic and asymptomatic patients, and the positioning of treatments in the treatment pathway. Study registration This study is registered as PROSPERO CRD42017055516. Funding The National Institute for Health Research Health Technology Assessment programme.

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Ga-68 prostate-specific membrane antigen-HBED-CC positron emission tomography/computed tomography in anaplastic thyroid carcinoma

et al. 2022

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Purpose: Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer and there is no established treatment that works well. The study was conducted to see prostate-specific membrane antigen (PSMA) expression in ATC as a stepping stone to study its role in potential theranostics. Materials and Methods: Pathologically proven ATC patients were prospectively included in this study. Ga-68-PSMA positron emission tomography/computed tomography (PET/CT) was done to look for PSMA expression in local and distant sites 45-60 mins after injecting 2-3mCi of tracer. Results: Twenty patients were enrolled in this study. Nodal metastases were seen in all patients, while distant metastases were seen in 17/20. The mean SUV max of primary lesion was 6.72 ± 4.6. Mean SUVmax of node and lung lesions was 5.7 ± 5.6 and 2.9 ± 1.98, respectively. Mean SUV max of liver, mediastinum, and parotid gland was 5.95 ± 3.03, 1.54 ± 0.68, and 9.03 ± 3.75, respectively. Mean Tumor to background ratio (liver = TBRl; mediastinum = TBRm; parotid = TBRp) were 1.21, 4.49 and 0.78, respectively. Conclusion: ATC showed variable PSMA expression on Ga-68-PSMA-PET/CT and this attribute may be potentially useful in ATC theranostics.

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Efficacy and safety of vascular endothelial growth factor receptor tyrosine kinase inhibitors in the treatment of advanced thyroid cancer: a meta-analysis of randomized controlled trials

Cited by 3 publications

References 48 publications

Risk of venous and arterial thromboembolic events associated with tyrosine kinase inhibitors in advanced thyroid cancer: a meta-analysis and systematic review

Risk of venous and arterial thromboembolic events associated with tyrosine kinase inhibitors in advanced thyroid cancer: a meta-analysis and systematic review

Lenvatinib and sorafenib for differentiated thyroid cancer after radioactive iodine: a systematic review and economic evaluation

Ga-68 prostate-specific membrane antigen-HBED-CC positron emission tomography/computed tomography in anaplastic thyroid carcinoma

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