Cabozantinib

A phase III, randomized, double blind, placebo-controlled study (COSMIC-311 [NCT03690388]) was conducted to evaluate the efficacy of cabozantinib in patients aged 16 years and older with RAI-refractory differentiated thyroid cancer. Objective response rate was the primary end point in the first 100 randomly assigned patients (the objective response rate intention-to-treat [OITT] population), and PFS was the primary end point in all randomly assigned patients (the intention-to-treat [ITT] population).[35]

A phase III, randomized, double blind, placebo-controlled study (COSMIC-311 [NCT03690388]) was conducted to evaluate the efficacy of cabozantinib in patients aged 16 years and older with RAI-refractory differentiated thyroid cancer. Objective response rate was the primary end point in the first 100 randomly assigned patients (the objective response rate intention-to-treat [OITT] population), and PFS was the primary end point in all randomly assigned patients (the intention-to-treat [ITT] population).[35]

Of 187 patients, 63% had received previous therapy with lenvatinib, 60% had received previous therapy with sorafenib, and 24% had received previous therapy with both lenvatinib and sorafenib. Most patients (76%) had experienced disease progression while receiving sorafenib or lenvatinib.

A phase III, randomized, double blind, placebo-controlled study (COSMIC-311 [NCT03690388]) was conducted to evaluate the efficacy of cabozantinib in patients aged 16 years and older with RAI-refractory differentiated thyroid cancer. Objective response rate was the primary end point in the first 100 randomly assigned patients (the objective response rate intention-to-treat [OITT] population), and PFS was the primary end point in all randomly assigned patients (the intention-to-treat [ITT] population).[35]

In the OITT population, 15% of patients (99% CI, 5.8%–29.3%) in the cabozantinib group had a confirmed partial response, and median duration of response had not been reached at the data cutoff.

A phase III, randomized, double blind, placebo-controlled study (COSMIC-311 [NCT03690388]) was conducted to evaluate the efficacy of cabozantinib in patients aged 16 years and older with RAI-refractory differentiated thyroid cancer. Objective response rate was the primary end point in the first 100 randomly assigned patients (the objective response rate intention-to-treat [OITT] population), and PFS was the primary end point in all randomly assigned patients (the intention-to-treat [ITT] population).[35]

In the ITT population, after a median follow-up of 6.2 months, patients who received cabozantinib showed significant improvement in PFS compared with patients who received placebo (median not reached [96% CI, 5.7–not estimable (NE)] vs. 1.9 months [1.8–3.6]) (HR, 0.22; 96% CI, 0.13–0.36; P < .0001). Median OS was not reached in either ITT group (95% CI, NE–NE) (HR, 0.54; 95% CI, 0.27–1.11). The 6-month OS rate was 85% (95% CI, 75%–91%) in the cabozantinib group and 73% (58.4%–83.7%) in the placebo group.

A phase III, randomized, double blind, placebo-controlled study (COSMIC-311 [NCT03690388]) was conducted to evaluate the efficacy of cabozantinib in patients aged 16 years and older with RAI-refractory differentiated thyroid cancer. Objective response rate was the primary end point in the first 100 randomly assigned patients (the objective response rate intention-to-treat [OITT] population), and PFS was the primary end point in all randomly assigned patients (the intention-to-treat [ITT] population).[35]

Grade 3 to 4 treatment-related adverse events occurred in 57% of patients who received cabozantinib and 26% of patients who received placebo, and included palmar-plantar erythrodysesthesia (10%), hypertension (11%), fatigue (8%), diarrhea (7%), and hypocalcemia (7%). Serious treatment-related adverse events occurred in 20 of 125 patients (16%) in the cabozantinib group and 1 of 62 patients (2%) in the placebo group. There were no treatment-related deaths.

A phase III, randomized, double blind, placebo-controlled study (COSMIC-311 [NCT03690388]) was conducted to evaluate the efficacy of cabozantinib in patients aged 16 years and older with RAI-refractory differentiated thyroid cancer. Objective response rate was the primary end point in the first 100 randomly assigned patients (the objective response rate intention-to-treat [OITT] population), and PFS was the primary end point in all randomly assigned patients (the intention-to-treat [ITT] population).[35]

In 2021, the FDA reviewed a new drug application for the use of cabozantinib in patients aged 12 years and older with differentiated thyroid cancer because there are no standard-of-care treatments for this population after anti-VEGFR therapy, such as lenvatinib or sorafenib.