Will There A New Standard for Care for Some Thyroid Cancers?
PHILADELPHIA  Cabozantinib might become a new standard of care in patients with previously treated differentiated thyroid cancer, according to a new study. The inhibitor of VEGFR2, MET, AXL, and RET showed clinical activity in patients with radioiodine (RAI)-refractory DTC in phase 1/2 studies. The phase 3 study, available at the 2021 American Society of Clinical Oncology (ASCO) annual meeting, evaluated the efficacy and safety of cabozantinib vs. placebo in RAI-refractory thyroid cancer patients who had progressed during or after prior VEGFR-targeted therapy.1  In the double-blind, phase 3 trial led by Abramson Cancer Center researchers from the University of Pennsylvania, patients were randomized 2:1 to receive 60 mg of cabozantinib daily or placebo, stratified by whether they had prior lenvatinib treatment and whether they were older or younger than 65. Participants with RAI-refractory DTC must have received lenvatinib or sorafenib for DTC and progressed during or following treatment with at least two prior VEGFR inhibitors, researchers explained. They added that patients randomized to placebo could cross over to open-label cabozantinib treatment upon disease progression per blinded independent radiology committee (BIRC). Defined as the studys primary endpoints were objective response rate (ORR) in the first 100 randomized patients and progression-free survival (PFS) in all randomized patients. As of Aug. 19, 2020, 125 patients had been randomized to the cabozantinib arm and 62 of the placebo arm. Participants had a median age of 66, 55% were female and 63% received prior Lenvatinib treatment, Median (m) follow-up was 6.2 months. Researchers explained that, at the planned interim analysis, the trial met the primary endpoint of progression-free survival with cabozantinib demonstrating significant improvement over placebo (HR 0.22, 96% CI 0.130.36; p < 0.0001). While mPFS was not reached for cabozantinib, it was 1.9 months for placebo. PFS benefit was observed in all prespecified subgroups including prior L (yes, HR 0.26; no, HR 0.11) and age (65 yr, HR 0.16; > 65 yr, HR 0.31), the study team advised. ORR was 15% for C vs 0% for P (p = 0.0281) but did not meet the prespecified criteria for statistical significance (p < 0.01). A favorable OS trend was observed for C vs P (HR 0.54, 95% CI 0.271.11).  Treatment-emergent adverse events (AEs) that had higher occurrences in the cabozantinib arm vs. placebo included diarrhea (51% vs 3%), hand-foot skin reaction (46% vs 0%), hypertension (28% vs 5%), fatigue (27% vs 8%), and nausea (24% vs 2%). Overall, the authors reported, grade 3/4 AEs were experienced by 57% of patients receiving cabozantinib vs. 26% with placebo. As a result, dose reductions due to any grade AEs occurred in 57% of patients in the cabozantinib arm, compared to 5% with placebo. In addition, treatment discontinuations due to AEs not related to disease progression occurred in 5% of patients on cabozantinib and none for the placebo. Researchers concluded that cabozantinib showed a clinically and statistically significant improvement in PFS over [placebo] in patients with RAI-refractory DTC after prior VEGFR-targeted therapy with no unexpected toxicities.