A lower daily dose of 60 mg cabozantinib (Cometriq®) for the treatment of medullary thyroid cancer (MTC) failed to meet the primary endpoint of phase 4 EXAMINER clinical trial (NCT01896479). The results of the trial were presented at the 90th Annual Meeting of the American Thyroid Association.
In the trial, patients were randomized 1:1 to receive either the lower 60 mg tablet dose of cabozantinib (Arm1) or receive the recommended dose of 140 mg capsule (Arm2). Arm1 failed to meet the primary endpoint of noninferiority in progression-free survival (PFS) per blinded independent radiology committee (BIRC) compared to Arm2.
Arm1 had a median PFS per BIRC of 11 months compared to 13.9 months in Arm2, which resulted in a hazard ratio (HR) of 1.24, but the upper limit of 95% CI (1.70) was above the prespecified threshold of 1.58.
The secondary study endpoint of objective response rate (ORR) was the same for both arms of the study (33%). Patients in Arm2 did have a slightly longer overall survival (OS) compared to Arm1 (33.0 months vs 29.4 months).
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The average treatment duration was slightly longer in Arm1 (11.07 months) compared to Arm2 (10.1 months). While the median average daily doses were not as high as the target doses due to dose reductions, patients in Arm2 did still receive higher doses than Arm1 (73.4 mg vs 38.7 mg). A lower rate of dose reduction was observed in Arm1 compared to Arm2 (69% vs 81%).
Adverse events (AEs) that emerged from treatment were nonsignificantly lower in Arm1 than Arm2 (63% vs 72%) and included diarrhea (16% vs 24%) and hand-foot skin reaction (7.3% vs 12%). However, fatigue was reported slightly higher in Arm1 (12% vs 6.5%). There was 1 death related to treatment in Arm2. Arm1 also had fewer discontinuations due to AEs (23% vs 36%).
A total of 247 patients were recruited for the trial with a median age of 60 years. Of the patients, 34% were female, 53% had M918T mutations in the RET gene, and 51% had received at least 1 prior systemic treatment for MTC.
“Both dose regimens showed activity in advanced MTC. However, the 60 mg tablet did not meet pre-specified non-inferiority criteria for PFS versus the 140 mg capsule,” the authors concluded.
Capdevila J, Klochikhin A, Leboulleux S, et al. Results of the Phase IV EXAMINER trial comparing two different cabozantinib formulations (60 mg tablet versus 140 mg capsule) in patients with progressive metastatic medullary thyroid cancer (MTC). Poster presented at: 90th Annual Meeting of the American Thyroid Association; October 1, 2021; Virtual.