3864 - Correlation of thyroglobulin (Tg) oscillations with progression-free survival (PFS) in patients with radioactive iodine-refractory (RAI-R) differentiated thyroid carcinoma (DTC) treated with multikinase inhibitors (MKI).

Background

Role of Tg levels as a biomarker in RAI-R DTC during MKI is unclear. Falling levels of Tg after starting MKI treatment has been previously reported, with a higher reduction in patients who achieve response. However, transient Tg oscillations are a common phenomenon during therapy without a clear correlation with progressive disease (PD). In the present study, we analyze the correlation between Tg oscillations and progression-free survival (PFS) in patients with RAI-R DTC during MKI treatment.

Methods

Thirty-seven consecutive patients were reviewed. Inclusion criteria were: pathology confirmed RAI-R DTC, age >18 years, MKI treatment in the first or second line and serial Tg determinations along with the follow-up. Variations in Tg levels during MKI treatment were evaluated. As exploratory hypothesis, we considered the “Tg elevation non-PD related”, defined as a significant elevation of Tg higher than 50% compared with previous measure, not related with PD by RECIST criteria, followed by a Tg reduction in a subsequent determination, in patients with an initial Tg reduction after starting MKI treatment.

Results

33 patients were included in the final analysis. Most MKI treatments were Sorafenib (44%), Lenvatinib (27%), Vandetanib (10%) and Axitinib (8%). Median duration of treatment was 15.5 months, and median PFS 20.2 months. Patients with any Tg levels reduction compared with baseline along MKI treatment showed a better PFS (23.5 vs. 3.6 months, p < 0.001). A Tg reduction >50% from baseline on the first month after starting MKI also had a benefit in PFS (27.7 vs. 14.2, p 0.02). 20.6% of cases had the nadir of Tg response beyond the first month of treatment. 34.4% of cases presented Tg elevation non-PD related along with follow-up (median number of elevations per patient: 2), with a better PFS compared with patients with other Tg oscillation patterns (29.9 vs. 15.5 months, p0.008).

Conclusions

Tg elevation non-PD related was associated with a better PFS compared with patients with other Tg variation patterns. Treatment with MKIs should not be stopped or changed based on Tg variations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

J. Hernando Cubero: Speaker Bureau / Expert testimony: Eisai, Ipsen, Roche, Angelini Pharma; Travel / Accommodation / Expenses: Ipsen, Novartis, AAA, Roche, AstraZeneca, Eisai. All other authors have declared no conflicts of interest.