Abstract
Single-agent PD-1 blockade demonstrated promising efficacy in advanced thyroid cancer. The phase II, single-arm, multi-cohort GETNE-DUTHY trial (clinicaltrials.gov NCT03753919, EudraCT 2018-001066-42) aimed to determine whether dual anti-PD-L1/CTLA-4 inhibition using durvalumab and tremelimumab can improve the clinical outcomes in advanced thyroid cancer. Three parallel cohorts including patients with differentiated thyroid carcinoma (Cohort 1, n = 37), medullary thyroid carcinoma (Cohort 2, n = 30), and anaplastic thyroid carcinoma (Cohort 3, n = 12) were recruited. Cohort 1 and 2 included patients following progression to previous standard systemic therapy and in Cohort 3 were recruited regardless of previous therapy. The primary endpoint was 6-month progression-free survival rate for Cohort 1 and 2 and 6-month overall survival rate for Cohort 3. Secondary endpoints included objective response rate, progression-free survival, overall survival, and safety. The 6-month progression-free survival rates were 32.4% (95% confidence interval [CI]: 20.4–51.6) (Cohort 1) and 40.8% (95% CI: 26.3–63.6) (Cohort 2); 6-month overall survival rate was 65.6% (95% CI: 43.2–99.8) (Cohort 3). The objective response rates were 8%, 10%, and 33% for Cohort 1, 2, and 3, respectively. No additional safety signals observed. Durvalumab plus tremelimumab treatment in patients with anaplastic thyroid carcinoma met the primary endpoint of this study, showing encouraging survival outcomes.
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The data that support the findings of this study are under restricted access for equivalent purposes for which the patients granted their consent to use the data (i.e. for research in thyroid carcinomas). Access can be obtained from the corresponding author (jcapdevila@vhio.net) upon request. Data will be provided anonymously, with no personal identifiable data. Data are available within the Article and Supplementary Information. Source data are provided with this paper.
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Acknowledgements
The authors thank all patients and families, investigators and study staff involved in the GETNE-DUTHY study; the MFAR Clinical Research team for regulatory, monitoring, and quality assurance activities; Guillem Marco Ph.D. and Pau Doñate Ph.D. for manuscript and language editing; and Emilio Pecharroman M.Sc. for statistical support. This study was sponsored by the Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE). AstraZeneca awarded a grant to GETNE to cover the study costs and provided the study medication. The funder had no role in the design or conduct of the study.
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J.C. conceived and designed the trial. All authors contributed in formal analysis, funding acquisition, investigation, project administration, resources, supervision, validation, visualization, and writing and finally approving of this paper.
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The authors declare the following competing interests: A.G.A. declares speakers’ bureau from EISAI Europe and Lilly; and travel, accommodations and expenses from Advanz, EISAI, Ipsen, ADACAP (Novartis), Amgen, Pfizer, Lilly. M.P.S. declares honoraria and payment for travel/accommodations/expenses from Eisai Europe, Merck Serono, and MSD. C.A.E. declares honoraria as speaker fees, served on advisory boards, and received sponsorship and accommodation at scientific meetings from Astra Zeneca, IPSEN, Pfizer, Bayer, and MSD. T.A.G. declares fees for speakers, consultancy, research, and other nonfinancial support from IPSEN, Eli Lilly, Adacap, Pfizer, EISAI, Bayer, Johnson & Johnson, Astellas-Pharma, Roche, BMS, and MSD. A.C.B. declares research and speaking grants from Esteve, speaking grants from Lilly, and travel grants from MSD, Roche and Amgen. N.B. declares consulting honoraria from Merck Serono, Bristol-Myers Squibb, Lilly, and Eisai; and travel/accommodation expenses from Merck Serono. E.S.G. declares honoraria as a consultant for GSK and research grants (institution) from GSK and Rgenta Therapeutics. The remaining co-authors declare no competing interests regarding this study.
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Capdevila, J., Hernando, J., Molina-Cerillo, J. et al. Durvalumab plus tremelimumab for the treatment of patients with progressive, refractory advanced thyroid carcinoma: the phase II GETNE-DUTHY trial. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71155-y
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DOI: https://doi.org/10.1038/s41467-026-71155-y
