TP53 Alterations Are Associated With Poor Response to Lenvatinib in Patients With Advanced Thyroid Cancer
Authors' conclusion
We show for the first time in advanced TC that the presence of TP53 alterations is a predictor of poor response to LEN treatment and is associated with worse PFS and OS rates. The evaluation of TP53 mutations/p53 expression might be included in the patient/tumor characterization to be performed before starting an MKI treatment.
Study context
- Population
- Patients with advanced thyroid cancer treated with lenvatinib (LEN); Thyroid cancer (TC) cell lines
- Participants
- 30 tumor tissues
- Exposure
- TP53-mutated vs TP53 wild-type tumors
- Outcome
- Response to LEN by TP53 mutation status
Methodological detailsvalidation cohort
- Validation cohort
Main finding
As reported in the abstract
Response to LEN
- TP53 mutations significantly correlated with a poor response to LEN
- TP53-mutated vs TP53 wild-type: P = 0.005
Observational data: associations, not effects.
Further findings
| Outcome | P value |
|---|---|
| PFS and OS by TP53 mutationTP53-mutated vs TP53 wild-type · shorter with TP53-mutated | P < 0.0001 |
| PFS and OS by TP53 mutationTP53-mutated vs TP53 wild-type · shorter with TP53-mutated | P = 0.0007 |
Progression-free survival (PFS) and overall survival (OS) by altered nuclear p53 protein expression
- Shorter PFS with altered nuclear p53 expression
- P = 0.0001
- Shorter OS with altered nuclear p53 expression
- P = 0.0056
Validation cohort
- Findings confirmed in a validation cohort
LEN sensitivity in TC cell lines
- Cell lines with p53 alterations had low or null sensitivity; TP53 wild-type lines showed varying sensitivity, mainly via increased G1-phase cells (cytostatic effect)
Original publication
TP53 Alterations Are Associated With Poor Response to Lenvatinib in Patients With Advanced Thyroid Cancer. J Clin Endocrinol Metab. Published 1 February 2025. doi:10.
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