KEY TAKEAWAYS
- The phase 3 COSMIC-311 trial evaluated the efficacy and safety of cabozantinib in individuals with previously treated RAIR-DTC.
- The trial’s primary endpoint was PFS evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 by a blinded, independent review.
- The trial involved randomizing patients aged 16 or above in a 2:1 ratio to receive oral cabozantinib tablets at 60 mg/day or a placebo.
- The trial achieved the primary endpoint, demonstrating that cabozantinib significantly improved PFS compared to a placebo.
- Treatment-emergent adverse events of grade 3/4 were observed in 62% and 28% of patients treated with cabozantinib and placebo, respectively.
- Cabozantinib exhibited sustained superior efficacy compared to a placebo in individuals with previously treated RAIR-DTC, with no emergence of novel safety signals.
At a median follow-up of 6.2 months with a sample size of 187, the phase 3 COSMIC-311 trial has successfully achieved the primary endpoint of progression-free survival (PFS). The study demonstrated that cabozantinib significantly improved PFS in comparison to a placebo (median, not reached vs. 1.9 months; P < .0001) in patients who have previously received treatment for radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). In this study, individuals aged 16 or above who were diagnosed with RAIR-DTC and had shown progression on prior lenvatinib and/or sorafenib were subjected to a randomization process in a 2:1 ratio. They were administered oral cabozantinib tablets at 60 mg/day or a placebo. Patients receiving a placebo may be eligible to switch to open-label cabozantinib treatment in the event of radiographic disease progression. The study’s primary endpoints were the objective response rate (ORR) in the first 100 randomized patients and the progression-free survival (PFS) in the intent-to-treat population. A blinded, independent review evaluated these according to the Response Evaluation Criteria in Solid Tumors version 1.1.
As of the data cutoff on February 8, 2021, a total of 258 patients were subjected to randomization, with 170 receiving cabozantinib and 88 receiving a placebo. The median follow-up duration was 10.1 months. The cabozantinib treatment group exhibited a median progression-free survival (PFS) of 11.0 months (96% confidence interval [CI], 7.4–13.8 months), while the placebo group exhibited a median PFS of 1.9 months (96% CI, 1.9–3.7 months). The hazard ratio was 0.22 (96% CI, 0.15–0.32; P < .0001). The objective response rate (ORR) was observed to be 11.0% (95% confidence interval [CI], 6.9%–16.9%) in comparison to 0% (95% CI, 0.0%–4.1%) (P = .0003) with the administration of cabozantinib. A single complete response was noted. Forty patients who were administered a placebo were subsequently switched to open-label cabozantinib. Treatment-emergent adverse events of grade 3/4 were observed in 62% and 28% of patients treated with cabozantinib and placebo, respectively. The most frequent adverse events were hypertension (12% vs. 2%), palmar-plantar erythrodysesthesia (10% vs. 0%), and fatigue (9% vs. 0%). No adverse events of grade 5 were observed concerning the treatment. Upon extended follow-up, cabozantinib exhibited sustained superior efficacy compared to a placebo in individuals with previously treated radioactive iodine refractory differentiated thyroid cancer, with no emergence of novel safety signals.
Source:https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34493#cncr34493-tbl-0001
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03690388
Brose, M. S., Robinson, B. G., Sherman, S. I., Jarzab, B., Lin, C., Vaisman, F., … Capdevila, J. (2022)./ Cabozantinib for previously treated radioiodine-refractory differentiated thyroid cancer: Updated results from the phase 3 COSMIC-311 trial/ Cancer, 128(24), 4203–4212. https://doi.org/10.1002/cncr.34493
