ESMO Clinical Practice Guideline update on the use of systemic therapy in advanced thyroid cancer
Cet article présente une mise à jour des recommandations de l'"European Society For Medical Oncology" concernant l'utilisation de traitements systémiques chez les patients atteints d'un cancer de la thyroïde de stade avancé
Between 2013 and 2015, a number of multikinase inhibitors (MKIs) targeting the vascular endothelial growth factor receptor (VEGFR) were approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) for the treatment of advanced/metastatic differentiated thyroid cancers (DTCs) (i.e. lenvatinib and sorafenib) and medullary thyroid cancers (MTCs) (i.e. cabozantinib and vandetanib), thus becoming the standard first-line systemic therapy in this setting.1 Head-to-head comparisons between the two pairs of drugs (i.e. lenvatinib versus sorafenib, and cabozantinib versus vandetanib) have never been undertaken, thus not allowing a hierarchy to be established between them. The use of these agents in a real-world setting is mainly influenced by the regulatory heterogeneity across countries. If all available, an individualised cost-effectiveness analysis that considers the differences in terms of effectiveness and safety profile helps to decide the order in which they should be used. After these MKIs entered the market, several studies emerged to verify and describe the drugs’ benefit.2, 3, 4 Data on real-life experiences, taken all together, provide evidence of their clinical effectiveness, and produce data on safety profiles that mimic those reported by the randomised clinical trials (RCTs). Substantial differences, however, emerge among studies in the magnitude of MKI effects and the incidence of some adverse events. This can largely be explained by the heterogeneity across the studies in inclusion criteria, sample size (small series are more prone to be influenced by outliers), drug doses, lengths of follow-up, assessment of disease progression and analysis of the outcome measures. Given the toxicities associated with MKIs, clinicians sometimes prefer to start treatment at a lower than approved dose. A recent RCT compared the efficacy and safety profile of lenvatinib at the approved starting dose (i.e. 24 mg per day) and at a lower starting dose (i.e. 18 mg per day) in a cohort of patients with metastatic/advanced DTC.5 Not surprisingly, the higher dose turned out to more effective, in that the objective response rate (ORR) was 57.3% [95% confidence interval (CI) 46.1%-68.5%] versus 40.3% (95% CI 29.3%-51.2%) in the lower dose group [odds ratio 0.50 (95% CI 0.26-0.96)]. The safety profile was comparable. Although these data cannot be generalised to the whole class of MKIs, it seems reasonable to state that the higher the dose, the greater the efficacy of these drugs. While this assumption supports using the MKIs’ approved starting dose to maximise their efficacy, the choice should be individualised based on the patient's performance status and comorbidities.
Annals of Oncology , article en libre accès, 2022