A Bayesian network meta-analysis: evaluating the efficacy and safety of targeted therapies in metastatic or advanced radioiodine-refractory differentiated thyroid cancer

TL;DR

This study compares the effectiveness and safety of different drugs for advanced thyroid cancer resistant to radioiodine, finding lenvatinib as the most promising option.

Contribution

A Bayesian network meta-analysis identifies lenvatinib as the top treatment for progression-free survival and response rate in radioiodine-refractory thyroid cancer.

Findings

Lenvatinib showed the highest progression-free survival and objective response rate among tested drugs.

Apatinib had early benefits but lost efficacy over time and ranked highest for safety.

No drug significantly improved overall survival compared to placebo.

Abstract

Approximately 5%–10% of patients with differentiated thyroid cancer (DTC) develop resistance to radioactive iodine (RAI), leading to unsatisfactory survival rates. The optimal medication for advanced or metastatic RAI-resistant differentiated thyroid cancer (RAIR-DTC) remains unclear.

We conducted a Bayesian network meta-analysis based on a systematic search of six electronic databases. The primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), objective response rate (ORR), and grade ≥3 adverse events (AEs). Hazard ratios (HRs) with 95% credible intervals (CrIs) were used for time-to-event outcomes, while odds ratios (ORs) with 95% CrIs were used for binary outcomes. A separate Bayesian network meta-analysis was performed for each endpoint.

Our study included 9 RCTs involving 1,760 patients with RAIR-DTC. Lenvatinib, anlotinib, apatinib, and cabozantinib all significantly improved PFS versus placebo (HRs: 3.85–5.36), with lenvatinib ranking first overall (SUCRA: 81.97%) and showing sustained benefit up to 24 months. Apatinib provided early PFS advantage but waning efficacy beyond 6–9 months. No treatment significantly improved OS, though apatinib consistently ranked highest for OS. Lenvatinib achieved the highest objective response rate (OR = 143.18; SUCRA: 82.09%). For grade ≥3 adverse events, no treatment differed significantly from placebo; however, apatinib ranked highest in safety (SUCRA = 93.16%).

Lenvatinib demonstrates the greatest benefit in both PFS and ORR among the evaluated TKIs for RAIR-DTC, suggesting it as a potential preferred first-line option. The time-dependent efficacy patterns of other TKIs warrant further investigation.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251089713, identifier CRD420251089713.

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