Abstract |
Background: Cabozantinib inhibits pathways involved in medullary thyroid cancer (MTC). Cabozantinib is approved as 140 mg/day in capsules for MTC and 60 mg/day in tablets for other solid tumors. This study compared the two doses in progressive metastatic MTC. Methods: In this Phase 4, randomized, double-blind noninferiority (NI) trial (NCT01896479), patients with progressive metastatic MTC were randomized 1:1 to cabozantinib 60 mg/day tablet or 140 mg/day capsules. The primary end point was progression-free survival (PFS) by blinded independent radiology committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. NI would be concluded if the upper 95% confidence interval [CI] for the PFS hazard ratio (HR) was less than the NI margin, 1.58. The secondary end point was objective response rate (ORR) by BIRC per RECIST v1.1; additional end points included safety and pharmacokinetics. Results: At data cutoff (July 15, 2020), 247 patients were randomized to the 60 mg/day tablet arm (n = 123) and the 140 mg/day capsules arm (n = 124). NI was not met (median PFS 11.0 months vs. 13.9 months in the 60 and 140 mg/day arms [HR 1.24; CI 0.90-1.70; p = 0.19]). The ORR was 33% in both arms. Generally, adverse event (AE) incidence was lower in the 60 mg/day arm (Grade 3/4, 63% vs. 72%), as were dose reductions (69% vs. 81%) and treatment discontinuations due to AEs (23% vs. 36%). Initially, cabozantinib plasma concentrations were higher in the 140 mg/day arm but became similar between arms at later time points. Conclusions: PFS NI of the cabozantinib 60 mg/day tablet vs. 140 mg/day capsules was not met. The 60 mg/day tablet had the same ORR and lower rates of AEs. Clinical Trial Registry: ClinicalTrials.gov NCT01896479.
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Authors | Jaume Capdevila, Arkadiy Klochikhin, Sophie Leboulleux, Pavel Isaev, Corin Badiu, Bruce Robinson, Brett G M Hughes, Bhumsuk Keam, Francis Parnis, Rossella Elisei, Pablo Gajate, Hui K Gan, Ellen Kapiteijn, Laura Locati, Milan Mangeshkar, Leonardo Faoro, Jolanta Krajewska, Barbara Jarzab |
Journal | Thyroid : official journal of the American Thyroid Association
(Thyroid)
Vol. 32
Issue 5
Pg. 515-524
(05 2022)
ISSN: 1557-9077 [Electronic] United States |
PMID | 35403447
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anilides
- Antineoplastic Agents
- Capsules
- Protein Kinase Inhibitors
- Pyridines
- Tablets
- cabozantinib
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Topics |
- Anilides
(adverse effects)
- Antineoplastic Agents
(therapeutic use)
- Capsules
(therapeutic use)
- Carcinoma, Neuroendocrine
(pathology)
- Humans
- Protein Kinase Inhibitors
(therapeutic use)
- Pyridines
- Tablets
(therapeutic use)
- Thyroid Neoplasms
(pathology)
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