Neoadjuvant anlotinib for locally advanced thyroid cancer: a single-arm phase II study (ALTER-T001)

Background Locally advanced thyroid cancer involving critical cervical structures is often not amenable to upfront surgery, and effective strategies are needed to improve surgical feasibility. ALTER-T001 study evaluated the safety, efficacy, and quality of life (QoL) of neoadjuvant anlotinib in this setting. Methods Patients with pathologically confirmed, locally advanced thyroid cancer not amenable to surgery received neoadjuvant anlotinib. “Not amenable to surgery” tumors included those unresectable, high-risk for surgery/recurrence, severely impairing QoL upon resection, or with limited adhesion to blood vessels, esophagus, or trachea. Primary endpoint was objective response rate (ORR). Secondary endpoints included time to response (TTR), disease control rate (DCR), actual operation rate, R0 resection rate, progression-free survival (PFS), QoL, and safety. Results In 50 DTC patients, ORR and DCR were 42.0% and 84.0% (48.8% and 97.7% in 43 evaluable cases). Median TTR was 2.8 months. Surgery occurred in 21 (42.0%) patients, yielding a 57.1% R0 rate. Median PFS in non-surgical patients was 29.8 months. The most frequent grade ≥3 treatment-related adverse event (TRAE) was hypertension (18.0%). TRAEs led to dose reductions and interruptions in 8 (16.0%) and 5 (10.0%) patients, respectively. No treatment-related deaths occurred. Global health status remained generally stable during early treatment, although deterioration in several function domains was observed. One MTC patient achieved R0 resection after 4 cycles and is presented separately as a descriptive case. Conclusion Neoadjuvant anlotinib exhibited acceptable efficacy, tolerability, and QoL profiles in locally advanced DTC not amenable to surgery, with potential to reduce tumor burden and facilitate conversion surgery. Larger MTC cohorts are needed to further evaluate the efficacy and safety of neoadjuvant anlotinib. Clinical Trial Registration https://www.chictr.org.cn/ , identifier ChiCTR2100048077.