Abstract 2220P
Background
Molecular alterations (MA) may drive therapeutic approaches, however no data of thyroid carcinoma are available in Spain. We report next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) results.
Methods
MOLTHY is an observational, retrospective, translational and multidisciplinary study aiming to characterize the MA of advanced radioiodine-refractory (RAI-R) differentiated thyroid carcinoma (DTC) and medullary thyroid carcinomas (MTC) from 12 Spanish referral centers. The primary objective characterizes the MA prevalence, demographic and prognostic characteristics of 150 patients (pts). MA were centrally analyzed by Oncomine focus (NGS), FISH for NTRK1/3 and RET genes, and NTRK by immunohistochemistry (IHC). Efficacy was assessed by objective response rate (ORR); event-free survival (EFS), defined as time to progression, death, or discontinuation due to toxicity; and overall survival (OS).
Results
From Nov 2021 to Feb 2023, 149 pts were included, 106 (71%) DTC and 43 (29%) MTC. The table shows pts characteristics, treatments, and MA. 1st-line systemic therapy (L) had been administered in 76 DTC pts (71.7%): 31.6% ORR (24/76), 18 months (mo) as median (m) EFS (95%CI:13.2-25) and mOS 293mo (95%CI:145.9-NR); and in 32 MTC pts (74.4%): 40.6% ORR (13/32), 41.5mo (16.4-NR) as mEFS with mOS not reached. RET fusions had no significant impact on the efficacy of 1st L in DTC. However, MTC pts carrying RET mutations showed a better 10-year cumulative OS (100%; 95% CI: 100-100) versus RET-naive (57.1%, 24.3-100); p=0.002; Cox). NTRK1/3 fusions didn’t show any impact on the efficacy of 1st unmatched-L.
Table: 2220P
DTC (106 pts) | MTC (43 pts) | |
Patients characteristics | ||
Median Age, years (95% CI) | 66 (61-70) | 58 (52-66) |
Sex, Female (%) | 57 (53.8) | 17 (39.5) |
Metastasis at diagnosis (%) | 39 (36.8) | 20 (46.5) |
Lymph node involvement at first surgery (%) | 52 (49.1%) | 30 (69.8%) |
Associated to inherited MEN2A Syndrome (%) | - | 8 (18.6%) |
MOLECULAR ALTERATIONS by NGS & FISH (%) | ||
RET alteration | 7 fusions (6.6) | 34 mutations (79) |
NTRK1 fusion | 1 (0.9) | - |
NTRK3 fusion | 2 (1.9) | - |
BRAF mutation | 41 (38.7) | - |
HRAS mutation | 4 (3.8) | 3 (7) |
KRAS mutation | 3 (2.8) | - |
NRAS mutation | 11 (10.4) | - |
PIK3CA mutation | 2 (1.9) | - |
1st-LINE TREATMENT: pts treated (%) | 76 | 32 |
Multikinase inhibitor | 72 (94.7) | 27 (84.4) |
Clinical trial | 3 (3.9) | 5 (15.6) |
Other | 1 (1.3) | - |
Conclusions
MOLTHY is the first and larger Spanish cohort of RAI-R DTC and MTC. The prevalence of RET fusions, BRAF/RAS/PIK3CA mutations and NTRK fusions in DTC are consistent with reported studies. RET-mutant MTC correlates with better OS, as previous studies have demonstrated with RET M918T carriers. NGS, FISH and IHC comparison is underway.
Clinical trial identification
NCT04970134.
Editorial acknowledgement
Legal entity responsible for the study
Grupo Español de Tratamiento de Tumores de Cabeza y Cuello (TTCC).
Funding
Research Grant SEOM/+1 Súmate (national and public grant).
Disclosure
N. Baste Rotllan: Non-Financial Interests, Advisory Role: Eisai, MSD, Merck Serono, BioNTech, Roche, BMS, Exelixis. J. Hernando: Financial Interests, Personal, Advisory Board: Eisai, Ipsen, Novartis, AAA, Angelini, Pfizer, Roche. J. Martínez Trufero: Financial Interests, Personal, Advisory Board, Advisory Board Meeting: Boehringer, Deciphera, Eisai, Eisai, GSK, PharmaMar; Financial Interests, Personal, Invited Speaker: Ipsen, Medicamenta, Merck, MSD, Roche; Non-Financial Interests, Institutional, Local PI, Clinical trial: Ayala Pharmaceuticals, Blueprint, Boehringer, Kariopharm Therapeutics, Lilly, Rain Therapeutics, Syneos Health; Financial Interests, Institutional, Local PI, Clinical trial: SynOx Therapeutics; Non-Financial Interests, Personal, Member of Board of Directors, Spanish group of Sarcoma Research: GEIS Group; Non-Financial Interests, Personal, Advisory Board, Spanish Group of Head and Neck cancer Research: TTCC Group. M. Plana Serrahima: Financial Interests, Institutional, Other: Nanobiotix; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: BMS. J. Rubió-Casadevall: Financial Interests, Personal, Advisory Board, Advisory Board in June 2020: Novartis; Financial Interests, Personal, Advisory Board, Advisory board in April 2021: Sanofi; Financial Interests, Personal, Advisory Board, Advisory board in March 2022: Merck; Financial Interests, Personal, Speaker, Consultant, Advisor, Speaker honoraria in December 2022: Novartis. E. Gallardo: Financial Interests, Personal, Advisory Board: Advanced Accelerator Applications, Astellas, AstraZeneca, Bayer, BMS, Daiichi Sankyo, Eisai, EUSA Pharma, GSK, Ipsen, Janssen, Lilly, Merck, Pfizer, Roche, Sanofi, Techdow; Financial Interests, Personal, Invited Speaker: Advanced Accelerator Applications, Astellas, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Eisai, EUSA Pharma, Ipsen, Janssen, Leo Pharma, Menarini, Merck, MSD, Pfizer, Roche, Rovi, Sanofi; Financial Interests, Personal, Expert Testimony: Merck, Novartis, Pfizer; Financial Interests, Institutional, Local PI: Astellas, AstraZeneca, Aveo, Bayer, BMS, Clovis, Daiichi Sankyo, Exelixis, Immunicum, Incyte, Ipsen, Janssen, Lilly, Mediolanum, Medivation, MSD, Novartis, Pfizer, Pfizer-Merck, QED Therapeutics, Roche, Seattle Genetics; Non-Financial Interests, Personal, Leadership Role, Member of the Board of Thrombosis and Cancer Section: SEOM; Non-Financial Interests, Personal, Leadership Role, Member of the Board: SOGUG. C. López López: Financial Interests, Personal, Invited Speaker: AAA, Amgen, AstraZeneca, Bayer, Eisai, Ipsen, Lilly, Merck, Novartis, Pfizer, Roche, Servier; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Eisai, Ipsen, Lilly, Merck, Pfizer, Roche, Servier; Financial Interests, Personal and Institutional, Research Grant: Amgen, AstraZeneca, Servier; Financial Interests, Personal, Funding: Bayer, Eisai, Lilly, Novartis, Pfizer, Roche; Financial Interests, Personal, Coordinating PI: Eisai, Ipsen; Financial Interests, Personal, Steering Committee Member: Ipsen; Financial Interests, Personal, Local PI: Ipsen, Roche. T. Alonso-Gordoa: Financial Interests, Personal, Advisory Board: Ipsen, Pfizer, Roche, Sanofi, Bayer, Eisai, Novartis, Lilly, Bristol Myers Squibb, Astellas; Financial Interests, Personal, Invited Speaker: Janssen; Non-Financial Interests, Project Lead: Pfizer, Ipsen. A. García-Álvarez: Financial Interests, Personal, Advisory Board: ADACAP; Other, Expense (Congress inscription): Advanz, Eisai, Ipsen, ADACAP. E. Ortega Izquierdo: Financial Interests, Personal, Invited Speaker: AstraZeneca, Clovis, Eisai, MSD, PharmaMar; Financial Interests, Personal, Expert Testimony: GSK. C. Teixido: Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck Sharp & Dohme, Roche Farma, Diaceutics, Pfizer, Janssen Oncology; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: Novartis. All other authors have declared no conflicts of interest.
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