Patients with radioiodine-refractory, differentiated thyroid cancer had a significant improvement in progression-free survival (PFS) when treated with cabozantinib in the phase 3 COSMIC-311 trial, which was presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
Cabozantinib provided a clinically significant improvement over placebo and may therefore be a new standard of care for patients with previously treated, differentiated thyroid cancer, according to Marcia S. Brose, MD, PhD, of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia, and colleagues.
Dr Brose and colleagues conducted this phase 3 study (ClinicalTrials.gov Identifier: NCT03690388) in which patients were randomized 2:1 to cabozantinib at 60 mg per day (n =125) or placebo (n = 62).
All patients were radioiodine-refractory, had previously received lenvatinib or sorafenib, and had progressed during or after treatment with 2 or fewer prior vascular endothelial growth factor receptor (VEGFR) inhibitors.
Patients assigned to placebo could cross over to cabozantinib at disease progression. The primary endpoints were objective response rate in the first 100 randomized patients and PFS in all randomized patients.
At an interim analysis with a median follow-up of 6.2 months, cabozantinib was associated with a significant improvement in PFS (hazard ratio [HR], 0.22; 95% CI, 0.13-0.36; P <.0001). The median PFS was not reached for cabozantinib and was 1.9 months for placebo.
Cabozantinib was associated with improved PFS in all prespecified subgroups, including in patients who had prior treatment with lenvatinib (HR, 0.26) and patients age 65 or younger (HR, 0.16).
Although cabozantinib resulted in a numerically higher overall response rate (15% vs 0%), the difference was not statistically significant. However, the researchers did note a favorable overall survival trend for cabozantinib compared with placebo (HR, 0.54; 95% CI, 0.27-1.11).
More than half (57%) of patients assigned to cabozantinib had dose reductions due to an adverse event of any grade, compared with 5% of patients assigned to placebo.
Treatment-emergent adverse events that were more common in the cabozantinib arm than in the placebo arm were diarrhea (51% vs 3%), hand-foot skin reaction (46% vs 0%), hypertension (28% vs 5%), fatigue (27% vs 8%), and nausea (24% vs 2%). No treatment-related deaths occurred.
Disclosures: This research was supported by Exelixis. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Brose MS, Robinson B, Sherman SI, et al. Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGF-targeted therapy: results from the phase 3 COSMIC-311 trial. J Clin Oncol. 2021;39:(suppl 15; abstr 6001). doi:10.1200/JCO.2021.39.15_suppl.6001
This article originally appeared on Cancer Therapy Advisor