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Title: A Randomized, Double-Blind Noninferiority Study to Evaluate the Efficacy of the Cabozantinib Tablet at 60 mg Per Day Compared with the Cabozantinib Capsule at 140 mg Per Day in Patients with Progressive, Metastatic Medullary Thyroid Cancer.
Austin Authors: Capdevila, Jaume;Klochikhin, Arkadiy;Leboulleux, Sophie;Isaev, Pavel;Badiu, Corin;Robinson, Bruce;Hughes, Brett G M;Keam, Bhumsuk;Parnis, Francis;Elisei, Rossella;Gajate, Pablo;Gan, Hui K ;Kapiteijn, Ellen;Locati, Laura;Mangeshkar, Milan;Faoro, Leonardo;Krajewska, Jolanta;Jarzab, Barbara
Affiliation: Austin Health
Medicine (University of Melbourne)
La Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australia
Royal North Shore Hospital, St Leonards, Australia
Royal Brisbane & Women's Hospital, and University of Queensland, Herston, Australia
Regional Clinical Oncology Hospital, Yaroslavl, Russian Federatio
Gustave Roussy and University Paris Saclay, Villejuif, France
Federal State Institution Medical Radiology Research Center, Obninsk, Russian Federation
"C. I. Parhon," National Institute of Endocrinology and "C. Davila" University of Medicine and Pharmacy, Bucharest, Romania
Seoul National University Hospital, Seoul, Republic of Korea
Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
Hospital Universitario Ramon y Cajal, Madrid, Spain
Leids Universitair Medisch Centrum, Leiden, The Netherlands
Istituto Nazionale Dei Tumori, Milano, Italy
Exelixis, Inc., Alameda, California, USA
M. Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland
Adelaide Cancer Centre, Kurralta Park, Australia
Vall Hebron University Hospital and Vall Hebron Institute of Oncology (VHIO), IOB-Quiron-Teknon, Barcelona, Spain
Issue Date: May-2022
Publication information: Thyroid 2022; 32(5): 515-524
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: NCT01896479.
DOI: 10.1089/thy.2022.0027
ORCID: 0000-0002-5333-9257
Journal: Thyroid : Official Journal of the American Thyroid Association
PubMed URL: 35403447
PubMed URL:
Type: Journal Article
Subjects: cabozantinib
medullary thyroid cancer
tyrosine kinase inhibitor
Appears in Collections:Journal articles

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