1935P - Sequence matters: Impact of first-line response in overall therapeutic outcome in differentiated thyroid cancer. Data from the Spanish national registry of thyroid cancer (REGETNE-Tiroides)

Background

Multikinase inhibitors (MKIs) are the main therapeutic option in the radioiodine-refractory (RAI-R) differentiated thyroid cancer (DTC) setting. Despite their widespread use, no consensus exists on the optimal MKI sequence, or on the criteria for selecting patients for the available first-line treatments.

Methods

A comprehensive review was conducted on all patients with a confirmed diagnosis of DTC in the REGETNE-Tiroides registry. This analysis explores the demographics, histological characteristics of the patient population, and treatment outcomes of different MKI treatment sequences.

Results

177 patients were included (70% women, 61 yo, 46% >65). A total of 155 (80%) patients received at least one TKI, 66 (42%) sorafenib and 52 (33%) lenvatinib as first-line therapy. 90 (58%) received second-line therapy (39% lenvatinib, 25% sorafenib, 20% cabozantinib). Of these, 39 (25%) received a third-line therapy and 10 (6%) received a fourth line of therapy. Median progression-free survival (mPFS) was 13, 9, 6 and 6 months for 1st, 2nd, 3rd and 4th line respectively, median overall survival (mOS) was 34, 39, 41 and 45 months. There was a significant difference in mOS between first-line responders and non-responders (34 vs 25 months, p=0.025). No other clinical or pathological characteristics were significant for mOS or first-line response. Patients with the best mOS received the following first-second line combinations: sorafenib-cabozantinib 42 m, lenvatinib- cabozantinib 36 m, sorafenib-lenvatinib 36 m, lenvatinib- sorafenib 21 m.

Conclusions

First-line response impacts on mOS in patients with RAI-R DTC. No clinical features distinctly predict those patients responding to MKI in a routine clinical practice setting. Addition of cabozantinib beyond the first line showed an interesting increase in mOS in this scenario. There remains a critical need to identify clinical, pathological, or molecular markers that allow us to select patients for the best MKI sequence. Further studies in the Spanish national registry are warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Pérez Fernandez: Financial Interests, Personal, Invited Speaker: FICIC. J. Hernando Cubero: Financial Interests, Personal, Advisory Board: Eisai, Ipsen, Novartis, AAA, Angelini, Pfizer, Roche. A. Garcia Alvarez: Financial Interests, Personal, Advisory Board: Adacap (Novartis); Other, Other, Expenses (Travel, Congress inscription): Advanz, Eisai, Ipsen, Adacap (Novartis). T. Alonso Gordoa: Financial Interests, Personal, Advisory Board: Ipsen, Pfizer, Roche, Sanofi, Bayer, Eisai, Novartis Advanced Accelerator Applications, Lilly, Bristol Myers Squibb, Astellas; Financial Interests, Personal, Invited Speaker: Janssen-Cilag; Non-Financial Interests, Project Lead: Ipsen, Pfizer, Johnson & Johnson. I. Ceballos Lenza: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Merck, MSD, BMS, ROCHE, AstraZeneca; Financial Interests, Personal, Advisory Board: Seagen, Novartis; Non-Financial Interests, Principal Investigator: BMS, GSK. M. Plana Serrahima: Financial Interests, Personal, Invited Speaker, X: MSD; Financial Interests, Personal, Invited Speaker: Eisai. E. Gallardo: Financial Interests, Personal, Advisory Board: Sanofi, Janssen, Astellas, Pfizer, Bayer, Roche, Ipsen, Eisai, EUSA Pharma, BMS, AstraZeneca, Merck, Merck, Daiichi Sankyo, Techdow, Novartis, Lilly, Pfizer, Advanced Accelerator Applications, GSK, Recordati; Financial Interests, Personal, Invited Speaker: Sanofi, Janssen, Astellas, Pfizer, Bayer, Roche, Ipsen, Eisai, EUSA Pharma, BMS, Merck, Daiichi Sankyo, MSD, Menarini, Rovi, Leo Pharma, Boehringer Ingelheim, Advanced Accelerator Applications; Financial Interests, Institutional, Local PI: Astellas, Medivation, Ipsen, Janssen, Pfizer, Lilly, Pfizer-Merck, MSD, BMS, Bayer, Daiichi Sankyo, Roche, AstraZeneca, Novartis, Seattle Genetics, Incyte, Aveo, Exelixis, Immunicum, Mediolanum, Clovis, QED Therapeutics, Debiopharm, Macrogenics; Non-Financial Interests, Principal Investigator, National (Spanish) coordinator for clinical trials: Anthos; Non-Financial Interests, Leadership Role, Member of the Board: SOGUG; Non-Financial Interests, Leadership Role, Member of the Board of Long Survivors Working Group: SEOM. J. Capdevila Castillon: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Ipsen, Ecelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Merck Serono; Financial Interests, Personal, Advisory Board: Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Merck Serono, Esteve, ITM; Financial Interests, Personal, Research Grant: AstraZeneca, Advanced Accelerator Applications, Bayer, Eisai, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Roche, Gilead; Financial Interests, Institutional, Coordinating PI: ITM, Boeringher. All other authors have declared no conflicts of interest.