ESMO Congress 2026

Cabozantinib is a multi-target tyrosine kinase inhibitor of VEGFR1/2/3, MET and AXL, with solid phase 3 evidence in its major indications: in a randomized, double-blind phase 3 trial in previously treated advanced hepatocellular carcinoma (707 patients, 2:1 randomization, cabozantinib 60 mg once daily versus placebo), median overall survival was 10.2 months versus 8.0 months, making cabozantinib one of the systemic therapies approved for HCC based on phase III trials ^[3][1], and positioning it in the second-line HCC setting alongside regorafenib and ramucirumab ^[4]; in advanced renal cell carcinoma, cabozantinib belongs to the class of agents with targets beyond VEGFR approved since 2015 ^[2], and a phase 3 trial of nivolumab plus cabozantinib versus sunitinib in the first line (651 patients) showed median progression-free survival of 16.6 months versus 8.3 months, HR 0.51 ^[6].

At this ESMO26 meeting, the Spanish GETNE group presented the GETNE-T2216/CABOTHYROID phase II trial (presented by @JHernando3): a total of 41 patients with radioiodine-refractory advanced thyroid cancer received cabozantinib. The numbers from the live posts: ORR 24% (the official GETNE post states 25.6%, a discrepancy between the two posts), DCR 89.7%, median PFS 16.1 months, and DoR 18.4 months; the study also reported an exploratory analysis of cfDNA methylation as potential predictive biomarkers.

Relative to existing knowledge, this readout extends cabozantinib's evidence base into thyroid cancer: the approvals and phase 3 evidence covered in the background literature are concentrated in HCC and RCC ^[1][2][3][6], whereas this presentation shows that single-agent cabozantinib delivered an objective response rate of roughly a quarter and disease control approaching 90% in radioiodine-refractory thyroid cancer, with a median PFS of 16.1 months that is numerically in the same range as the 16.6 months seen with the cabozantinib combination in RCC ^[6] (a cross-indication reference only, not a direct comparison). If the cfDNA methylation findings are validated in subsequent studies, they could point the way toward patient enrichment for this drug.

A few limitations should be noted: this is a phase II study with a small sample of only 41 patients; the live posts did not disclose overall survival data, control-arm design, or safety details; the ORR was reported as 24% in one post and 25.6% in the other, pending confirmation against the official abstract; and the cfDNA methylation analysis is exploratory in nature, with its predictive value yet to be confirmed.