Increased progression-free survival with cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer irrespective of prior VEGFR-targeted therapy and tumor histology: a subgroup analysis of the COSMIC-311 study.

BACKGROUND

Lenvatinib and sorafenib are standard-of-care first-line treatments for advanced, radioiodine-refractory differentiated thyroid cancer (DTC). However, most patients eventually become treatment-resistant and require additional therapies. The phase 3 COSMIC-311 study (NCT03690388) investigated cabozantinib in patients with radioiodine-refractory DTC who progressed on lenvatinib, sorafenib, or both and showed that cabozantinib provided substantial clinical benefit. Presented here is an analysis of COSMIC-311 based on prior therapy and histology.

METHODS

Patients were randomized 2:1 (stratification: prior lenvatinib [yes/no]; age [≤65, >65 years]) to oral cabozantinib (60-mg tablet/day) or matched placebo. Eligible patients received 1-2 prior vascular endothelial growth factor receptor (VEGFR)-targeting tyrosine kinase inhibitors for DTC (lenvatinib or sorafenib required), had a confirmed DTC diagnosis, and were refractory to or ineligible for radioiodine therapy. For this analysis, progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors v1.1 by a blinded independent radiology committee were evaluated by prior therapy (lenvatinib only, sorafenib only, both) and histology (papillary, follicular, oncocytic, poorly differentiated).

RESULTS

258 patients were randomized (170 cabozantinib/88 placebo) who previously received sorafenib only (n=96), lenvatinib only (n=102), or both (n=60). The median follow-up was 10.1 months. Median PFS (months) with cabozantinib/placebo was 16.6/3.2 (sorafenib only; hazard ratio [HR] 0.13 [95% confidence interval {CI} 0.06-0.26]), 5.8/1.9 (lenvatinib only; HR 0.28 [95% CI 0.16-0.48]), and 7.6/1.9 (both; HR 0.27 [95% CI 0.13-0.54]). ORR with cabozantinib/placebo was 21%/0% (sorafenib only), 4%/0% (lenvatinib only), and 8%/0% (both). Disease histology consisted of 150 papillary and 113 follicular, including 43 oncocytic and 36 poorly differentiated. The median PFS (months) with cabozantinib/placebo was 9.2/1.9 (papillary; HR 0.27 [95% CI 0.17-0.43]), 11.2/2.5 (follicular; HR 0.18 [95% CI 0.10-0.31]), 11.2/2.5 (oncocytic; HR 0.06 [95% CI 0.02-0.21]), and 7.4/1.8 (poorly differentiated; HR 0.18 [95% CI 0.08-0.43]). ORR with cabozantinib/placebo was 15%/0% (papillary), 8%/0% (follicular), 11%/0% (oncocytic), and 9%/0% (poorly differentiated). Safety outcomes evaluated were consistent with those previously observed for the overall population.

CONCLUSIONS

Results indicate that cabozantinib benefits patients with radioiodine-refractory DTC, regardless of prior lenvatinib or sorafenib treatments or histology.