Cabozantinib plus ipilimumab/nivolumab fails to meet efficacy target in thyroid cancer

Treatment with cabozantinib in combination with nivolumab and ipilimumab (CaboNivoIpi) results in low objective response rates (ORRs) and a high rate of grade ≥3 treatment-related adverse events (AEs) among patients with previously treated advanced differentiated thyroid cancer, reveals a recent study.

Eleven patients (median age 69 years) were included, with a median follow-up of 7.9 months. These patients were previously exposed to vascular endothelial growth factor (VEGF) receptor-targeted therapies such as lenvatinib, pazopanib, and sorafenib plus everolimus.

Among 10 evaluable patients, only one showed partial response (ORR within the first 6 months of treatment, 10 percent). The median progression-free survival was 9 months (95 percent confidence interval [CI], 3.0–not reached), while the median overall survival was 19.2 months (95 percent CI, 4.6–not reached).

Six (55 percent) of the 11 patients had grade 3/4 treatment-related AEs, while two (18 percent) had grade 5 AEs. Hypertension was the most common treatment-related AE.

"The study did not reach its prespecified efficacy threshold,” the investigators said.

In this study, patients with radioactive iodine-refractory differentiated thyroid cancer who progressed on 1 prior line of VEGF receptor-targeted therapy received a 2-week run-in of cabozantinib monotherapy followed by CaboNivoIpi for 4 cycles (cycle length, 6 weeks), followed by cabozantinib plus nivolumab (cycle length=4 weeks) until disease progression.

ORR within the first 6 months of treatment served as the primary endpoint. A Simon optimal two-stage design allowed for an interim analysis following the enrolment of 10 patients. At least five responses were necessary to proceed to stage 2.