Researchers from Vall d’Hebron University Hospital presented advances in targeted therapies for patients with thyroid cancer during the ESMO Congress 2026.
Updated results of the phase III LIBRETTO-531 trial showed durable benefits with selpercatinib compared with existing targeted therapies for patients with advanced RET-mutant medullary thyroid cancer (Abstract 4208O). Additionally, primary results from a phase II trial demonstrated safety and antitumor activity for sacituzumab govitecan-hziy in patients with advanced or metastatic differentiated or anaplastic thyroid carcinoma (Abstract 4209O).
LIBRETTO-531
Selpercatinib is a highly selective and potent RET inhibitor that was approved for the treatment of patients with advanced or metastatic medullary thyroid cancer with a RET mutation based on earlier findings from the randomized phase III LIBRETTO-531 trial. In LIBRETTO-531, first-line selpercatinib was compared with physician's choice of cabozantinib or vandetanib. Endpoints included overall survival, investigator-assessed progression-free survival, second progression-free survival, and safety.
“RET mutations are present in more than 50% of sporadic cases of advanced medullary thyroid cancer and in nearly all cases of medullary thyroid cancer associated with hereditary syndromes,” explained presenting author Jaume Capdevila, MD, PhD, a medical oncologist at Vall d’Hebron University Hospital and head of the Vall d’Hebron Institute of Oncology's Hepatobiliary, Pancreatic, and Endocrine Tumors Group.
As of the January 12, 2026, data cutoff, 61% of patients in the selpercatinib arm (n = 193) were continuing study treatment compared with 9% in the physician's choice arm (n = 98). Investigator-assessed 3-year progression-free survival rates were 75% with selpercatinib vs 25% with cabozantinib or vandetanib (hazard ratio [HR] = 0.21; 95% confidence interval [CI] = 0.14–0.30; P < .0001).
Patients were followed for overall survival for a median of 45.4 months in the investigational arm and 47 months in the control group. Three-year overall survival rates were 92% with selpercatinib vs 75% with cabozantinib or vandetanib (HR = 0.34; 95% CI = 0.19–0.59; P < .0001); at 4 years, overall survival rates were 87.1% and 66.8%, respectively.
Second progression-free survival also favored selpercatinib over cabozantinib or vandetanib. Disease progression was the main reason for discontinuation, accounting for 11% of the investigational arm and 41% of the control arm. Forty-four percent of patients in the control arm who progressed crossed over to receive selpercatinib.
Adverse events were considered manageable overall. Grade 3 or higher treatment-emergent adverse events were reported in 69% of patients in the selpercatinib arm and in 81% of patients in the physician's choice arm. Common treatment-emergent adverse events with selpercatinib included hypertension (50%), dry mouth (38%), and diarrhea (33%), compared with diarrhea (65%), palmar-plantar erythrodysesthesia syndrome (44%), and hypertension (42%) with cabozantinib or vandetanib. Eight percent of patients in the investigational arm discontinued due to treatment vs 32% in the control arm.
“These results reinforce the importance of screening for RET alterations in patients with medullary thyroid carcinoma and support the use of selpercatinib as the standard first-line treatment for patients with advanced RET-mutated medullary thyroid carcinoma,” Dr. Capdevila said.
SETHY
Sacituzumab govitecan is an antibody-drug conjugate targeting TROP2, which is highly expressed in both differentiated and anaplastic thyroid carcinoma and is associated with poor prognostic characteristics in both disease subtypes.
“Differentiated thyroid carcinoma accounts for more than 90% of cases and typically has a favorable prognosis; however, approximately 5% to 10% of patients develop metastases, and treatment becomes particularly complex when the disease stops responding to radioactive iodine. Anaplastic thyroid carcinoma, on the other hand, accounts for about 1% to 2% of cases and is characterized by rapid progression and high aggressiveness,” explained principal investigator and presenting author Alejandro Garcia-Alvarez, MD, MSc, an oncologist and researcher in the Hepatobiliary, Pancreatic, and Endocrine Tumors Group.
The single-arm, multicenter, two-stage phase II SETHY trial explored the use of sacituzumab govitecan in patients with radioactive iodine refractory differentiated thyroid carcinoma after progression on/after one to three prior systemic therapies in one cohort and in patients with anaplastic thyroid carcinoma who were treated in the first- or second-line setting in a second cohort. Patients were enrolled regardless of their TROP2 expression levels. The primary endpoint was confirmed objective response rate.
Both cohorts surpassed the first stage; more patients with anaplastic thyroid carcinoma were allowed to be enrolled.
In the differentiated thyroid carcinoma cohort (n = 24), the confirmed objective response rate was 4.4% and the median progression-free survival was 5.5 months, with a 12-month progression-free survival rate of 33.5%. Those with progression-free survivals beyond 12 months tended to have papillary or poorly differentiated histologies.
In the anaplastic thyroid carcinoma cohort (n = 13), the confirmed objective response rate was 16.7% and the median progression-free survival was 2.9 months.
The most common grade 3/4 adverse events with sacituzumab govitecan were diarrhea (16%), asthenia (11%), and neutropenia (8%).
“These findings support further research into the clinical development of sacituzumab govitecan in patients selected based on biomarkers and justify exploring combination strategies, including immunotherapy,” Dr. Garcia-Alvarez said.
DISCLOSURES: Funding for the LIBRETTO-531 trial came from Eli Lilly and Company. Funding for the SETHY trial came from GETNE through industry collaborator Gilead. For full disclosures of the authors from both studies, visit ctimeetingtech.com/esmo2026.
