Kinase-inhibitors for iodine-refractory differentiated thyroid cancer: still far from a structured therapeutic
Vincenzo Marotta1, Maria Grazia Chiofalo1, Francesca Di Gennaro2
1Struttura Complessa Chirurgia Oncologica Della Tiroide, Istituto Nazionale Tumori - Irccs - Fondazione G.Pascale, Napoli, Italy.
Abstract:
The kinase-inhibitors (KIs) sorafenib and lenvatinib demonstrated efficacy in iodine-refractory DTC upon phase III studies. However, evidence allowing a punctual balance of benefits and risks is poor. Furthermore, the lack of a direct comparison hampers to establish the proper sequence of administration. However, some insights may provided: a) indirect comparison between phase III trials showed milder toxicity for sorafenib, which should be preferred in case of cardiovascular comorbidities; b) prospective evidence of efficacy in KIs pre-treated patients is available only for lenvatinib, which should be used as second-line. Promising activity was found for the majority of other tested KIs, but no placebo-controlled trials are available. Emerging, but still early, frontiers include the restoration of iodine-sensitivity and the selective activity on pathogenic mutations. In conclusion, the use of KIs in iodine-refractory DTC is far from a structured therapeutic algorithm.
Insights
Kinase inhibitors (KIs) show promise for iodine-refractory DTC, but direct comparisons are lacking. Lenvatinib is preferred for second-line treatment, while sorafenib may be better for patients with cardiovascular issues.
Area of Science:
- Oncology
- Pharmacology
Background:
- Iodine-refractory differentiated thyroid cancer (DTC) presents treatment challenges.
- Kinase inhibitors (KIs) like sorafenib and lenvatinib have shown efficacy in phase III studies.
Purpose of the Study:
- To provide a balanced overview of benefits and risks of KIs in iodine-refractory DTC.
- To guide the optimal sequencing of KI administration.
Main Methods:
- Indirect comparison of phase III trial data for sorafenib and lenvatinib.
- Review of prospective evidence for KIs in pre-treated patients.
- Assessment of emerging therapeutic strategies.
Main Results:
- Sorafenib demonstrated milder toxicity in indirect comparisons, suggesting its use in patients with cardiovascular comorbidities.
- Lenvatinib has prospective evidence for efficacy in KI-pre-treated patients, supporting its second-line use.
- Other KIs show promising activity, but lack placebo-controlled trial data.
Conclusions:
- A structured therapeutic algorithm for KIs in iodine-refractory DTC is currently lacking.
- Evidence suggests lenvatinib as a second-line option and sorafenib for specific patient profiles.
- Further research, including placebo-controlled trials, is needed to optimize KI use.
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