Durvalumab plus tremelimumab for the treatment of patients with progressive, refractory advanced thyroid carcinoma: the phase II GETNE-DUTHY trial.

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.